Faculty Profiles - NAGAYOSHI Mako

Papers - NAGAYOSHI Mako

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A genome-wide association study on adherence to low-carbohydrate diets in Japanese. Invited Reviewed International journal

Yasuyuki Nakamura, Takashi Tamura, Akira Narita, Atsushi Shimizu, Yoichi Sutoh, Naoyuki Takashima, Kenji Matsui, Naoko Miyagawa, Aya Kadota, Katsuyuki Miura, Jun Otonari, Hiroaki Ikezaki, Asahi Hishida, Mako Nagayoshi, Rieko Okada, Yoko Kubo, Keitaro Tanaka, Chisato Shimanoe, Rie Ibusuki, Daisaku Nishimoto, Isao Oze, Hidemi Ito, Etsuko Ozaki, Daisuke Matsui, Haruo Mikami, Miho Kusakabe, Sadao Suzuki, Miki Watanabe, Kokichi Arisawa, Sakurako Katsuura-Kamano, Kiyonori Kuriki, Masahiro Nakatochi, Yukihide Momozawa, Michiaki Kubo, Kenji Takeuchi, Kenji Wakai

European journal of clinical nutrition Vol. 76 ( 8 ) page： 1103 - 1110 2022.8

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND/OBJECTIVES: Low-carbohydrate diets (LCD) are useful for weight reduction, and 50-55% carbohydrate consumption is associated with minimal risk. Genetic differences were related to nutritional consumption, food preferences, and dietary patterns, but whether particular genetic differences in individuals influence LCD adherence is unknown. SUBJECTS/METHODS: We conducted a GWAS on adherence to LCD utilizing 14,076 participants from the Japan Multi-Institutional Collaborative Cohort study. We used a previously validated semiquantitative food frequency questionnaire to estimate food consumption. Association of the imputed variants with the LCD score by Halton et al. we used linear regression analysis adjusting for sex, age, total dietary energy consumption, and components 1 to 10 by principal component analysis. We repeated the analysis with adjustment for alcohol consumption (g/day) in addition to the above-described variables. RESULTS: Men and women combined analysis without adjustment for alcohol consumption; we found 395 variants on chromosome 12 associated with the LCD score having P values <5 × 10-8. A conditional analysis with the addition of the dosage data of rs671 on chromosome 12 as a covariate, P values for all 395 SNPs on chromosome 12 turned out to be insignificant. In the analysis with additional adjustment for alcohol consumption, we did not identify any SNPs associated with the LCD score. CONCLUSION: We found rs671 was inversely associated with adherence to LCD, but that was strongly confounded by alcohol consumption.

DOI： 10.1038/s41430-022-01090-w

Associations of metabolic syndrome and metabolically unhealthy obesity with cancer mortality: The Japan Multi-Institutional Collaborative Cohort (J-MICC) study. Invited Reviewed International coauthorship International journal

Tien Van Nguyen, Kokichi Arisawa, Sakurako Katsuura-Kamano, Masashi Ishizu, Mako Nagayoshi, Rieko Okada, Asahi Hishida, Takashi Tamura, Megumi Hara, Keitaro Tanaka, Daisaku Nishimoto, Keiichi Shibuya, Teruhide Koyama, Isao Watanabe, Sadao Suzuki, Takeshi Nishiyama, Kiyonori Kuriki, Yasuyuki Nakamura, Yoshino Saito, Hiroaki Ikezaki, Jun Otonari, Yuriko N Koyanagi, Keitaro Matsuo, Haruo Mikami, Miho Kusakabe, Kenji Takeuchi, Kenji Wakai

PloS one Vol. 17 ( 7 ) page： e0269550 2022.7

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: The association between metabolic syndrome (MetS) and the risk of death from cancer is still a controversial issue. The purpose of this study was to examine the associations of MetS and metabolically unhealthy obesity (MUHO) with cancer mortality in a Japanese population. METHODS: We used data from the Japan Multi-Institutional Collaborative Cohort Study. The study population consisted of 28,554 eligible subjects (14,103 men and 14,451 women) aged 35-69 years. MetS was diagnosed based on the criteria of the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) and the Japan Society for the Study of Obesity (JASSO), using the body mass index instead of waist circumference. The Cox proportional hazards analysis was used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for total cancer mortality in relation to MetS and its components. Additionally, the associations of obesity and the metabolic health status with cancer mortality were examined. RESULTS: During an average 6.9-year follow-up, there were 192 deaths from cancer. The presence of MetS was significantly correlated with increased total cancer mortality when the JASSO criteria were used (HR = 1.51, 95% CI 1.04-2.21), but not when the NCEP-ATP III criteria were used (HR = 1.09, 95% CI 0.78-1.53). Metabolic risk factors, elevated fasting blood glucose, and MUHO were positively associated with cancer mortality (P <0.05). CONCLUSION: MetS diagnosed using the JASSO criteria and MUHO were associated with an increased risk of total cancer mortality in the Japanese population.

DOI： 10.1371/journal.pone.0269550

Associations Between Occupational Status, Support at Work, and Salivary Cortisol Levels Invited Reviewed

Kumi Hirokawa, Tetsuya Ohira, Masanori Nagao, Mako Nagayoshi, Mitsugu Kajiura, Hironori Imano, Akihiko Kitamura, Masahiko Kiyama, Takeo Okada, Hiroyasu Iso

International Journal of Behavioral Medicine Vol. 29 ( 3 ) page： 299 - 307 2022.6

The association of reproductive history with hypertension and obesity according to menopausal status: the J-MICC Study. Invited Reviewed International journal

Mizuki Ohashi, Katsuyuki Miura, Naoyuki Takashima, Aya Kadota, Yoshino Saito, Shunichiro Tsuji, Takashi Murakami, Yuka Kadomatsu, Mako Nagayoshi, Megumi Hara, Keitaro Tanaka, Takashi Tamura, Asahi Hishida, Toshiro Takezaki, Ippei Shimoshikiryo, Etsuko Ozaki, Isao Watanabe, Sadao Suzuki, Miki Watanabe, Kiyonori Kuriki, Kokichi Arisawa, Sakurako Katsuura-Kamano, Sho Yamasaki, Hiroaki Ikezaki, Isao Oze, Yuriko N Koyanagi, Haruo Mikami, Yohko Nakamura, Kenji Takeuchi, Yoshikuni Kita, Kenji Wakai

Hypertension research : official journal of the Japanese Society of Hypertension Vol. 45 ( 4 ) page： 708 - 714 2022.4

Language：English Publishing type：Research paper (scientific journal)

Previous studies have reported that the number of pregnancies and childbirths affected the risk of cardiovascular diseases (CVDs). However, the influence of reproductive history on hypertension and obesity, which are important risk factors for CVDs, is still unclear. Moreover, this association may vary depending on menopausal status. We evaluated the association of reproductive history with hypertension and obesity using a large cross-sectional dataset from the Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study). At the baseline survey, physical data, blood samples, and self-reported health questionnaires were collected. Participants with insufficient data were excluded, and 24,558 women from eight study regions were included in this study. Logistic regression analysis was conducted to evaluate the association of reproductive history with hypertension and obesity using multivariable-adjusted odds ratios. In premenopausal women, childbirth showed a generally protective effect on hypertension but not on obesity. In postmenopausal women, childbirth was positively associated with obesity and hypertension but not with hypertension after adjusting for BMI. In conclusion, reproductive history was associated with hypertension and obesity in a large Japanese population, and this association differed between premenopausal and postmenopausal women.

DOI： 10.1038/s41440-021-00820-0

Investigation of miRNA expression profiles using cohort samples reveals potential early detectability of colorectal cancers by serum miR-26a-5p before clinical diagnosis. Invited Reviewed International journal

Asahi Hishida, Hiroya Yamada, Yoshitaka Ando, Yoshinaga Okugawa, Manabu Shiozawa, Yohei Miyagi, Yataro Daigo, Yuji Toiyama, Yumiko Shirai, Koji Tanaka, Yoko Kubo, Rieko Okada, Mako Nagayoshi, Takashi Tamura, Atsuyoshi Mori, Takaaki Kondo, Nobuyuki Hamajima, Kenji Takeuchi, Kenji Wakai

Oncology letters Vol. 23 ( 3 ) page： 87 - 87 2022.3

Language：English Publishing type：Research paper (scientific journal)

Previous studies have investigated the usefulness of microRNA (miRNA/miR) expression data for the early detection of colorectal cancer (CRC). However, limited data are available regarding miRNAs that detect CRC before clinical diagnoses. Accordingly, the present study investigated the early detectability of CRC by miRNAs using the preserved serum samples of the cohort participants affected with CRC within 2 years of study enrollment. First, the significant miRNAs were revealed using clinical CRC samples for a (seven early CRCs and seven controls) microarray analysis based on significance analysis of microarrays. Next, replicability was verified by reverse transcription-quantitative (RT-q)PCR (eight early CRCs and eight controls, together with 12 CRCs and 12 controls). Finally, early detectability was tested using the cohort samples of Japan Multi-Institutional Collaborative Cohort Study (17 CRCs and 17 controls) to reveal how a certain number of patients developed CRC within 2 years after participation. In the discovery phase, miRNA expression measurements were conducted using a 3D-Gene Human miRNA Oligo Chip for 2,555 miRNAs, and RT-qPCR analyses were performed to validate the replicability. In the first validation set with eight CRCs with early clinical stage and eight age- and gender-matched controls, miR-26a-5p and miR-223-3p demonstrated the highest diagnostic accuracy of area under the curve (AUC)=1.000 (sensitivity and specificity 100%). In an examination of the predictability of CRC incidence using pre-clinical cohort samples, miR-26a-5p demonstrated good predictability of advanced CRC incidence with an AUC of 0.840. Overall, the present study revealed serum miR-26a-5p as a potential early detection marker for CRC.

DOI： 10.3892/ol.2022.13207

Associations of breastfeeding history with metabolic syndrome and cardiovascular risk factors in community-dwelling parous women: The Japan Multi-Institutional Collaborative Cohort Study. Invited Reviewed International journal

Takashi Matsunaga, Yuka Kadomatsu, Mineko Tsukamoto, Yoko Kubo, Rieko Okada, Mako Nagayoshi, Takashi Tamura, Asahi Hishida, Toshiro Takezaki, Ippei Shimoshikiryo, Sadao Suzuki, Hiroko Nakagawa, Naoyuki Takashima, Yoshino Saito, Kiyonori Kuriki, Kokichi Arisawa, Sakurako Katsuura-Kamano, Nagato Kuriyama, Daisuke Matsui, Haruo Mikami, Yohko Nakamura, Isao Oze, Hidemi Ito, Masayuki Murata, Hiroaki Ikezaki, Yuichiro Nishida, Chisato Shimanoe, Kenji Takeuchi, Kenji Wakai

PloS one Vol. 17 ( 1 ) page： e0262252 2022.1

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: The aim of the present study was to investigate the associations between breastfeeding and the prevalence of metabolic syndrome in community-dwelling parous women and to clarify whether the associations depend on age. METHODS: The present cross-sectional study included 11,118 women, aged 35-69 years. Participants' longest breastfeeding duration for one child and their number of breastfed children were assessed using a self-administered questionnaire, and their total breastfeeding duration was approximated as a product of the number of breastfed children and the longest breastfeeding duration. The longest and the total breastfeeding durations were categorized into none and tertiles above 0 months. Metabolic syndrome and cardiovascular risk factors (obesity, hypertension, dyslipidemia, and hyperglycemia) were defined as primary and secondary outcomes, respectively. Associations between breastfeeding history and metabolic syndrome or each cardiovascular risk factor were assessed using multivariable unconditional logistic regression analysis. RESULTS: Among a total of 11,118 women, 10,432 (93.8%) had ever breastfed, and 1,236 (11.1%) had metabolic syndrome. In participants aged <55 years, an inverse dose-response relationship was found between the number of breastfed children and the prevalence of metabolic syndrome; multivariable-adjusted odds ratios for 1, 2, 3, and ≥4 breastfed children were 0.60 (95% confidence interval [CI]: 0.31 to 1.17), 0.50 (95% CI: 0.29 to 0.87), 0.44 (95% CI: 0.24 to 0.84), and 0.35 (95% CI: 0.14 to 0.89), respectively. The longest and total breastfeeding durations of longer than 0 months were also associated with lower odds of metabolic syndrome relative to no breastfeeding history in participants aged <55 years. In contrast, all measures of breastfeeding history were not significantly associated with metabolic syndrome and cardiovascular risk factors in participants aged ≥55 years old. CONCLUSIONS: Breastfeeding history may be related to lower prevalence of metabolic syndrome in middle-aged parous women.

DOI： 10.1371/journal.pone.0262252

Study profile of the Japan Multi-institutional Collaborative Cohort (J-MICC) Study. Invited Reviewed

Kenji Takeuchi, Mariko Naito, Sayo Kawai, Mineko Tsukamoto, Yuka Kadomatsu, Yoko Kubo, Rieko Okada, Mako Nagayoshi, Takashi Tamura, Asahi Hishida, Masahiro Nakatochi, Tae Sasakabe, Shuji Hashimoto, Hidetaka Eguchi, Yukihide Momozawa, Hiroaki Ikezaki, Masayuki Murata, Norihiro Furusyo, Keitaro Tanaka, Megumi Hara, Yuichiro Nishida, Keitaro Matsuo, Hidemi Ito, Isao Oze, Haruo Mikami, Yohko Nakamura, Miho Kusakabe, Toshiro Takezaki, Rie Ibusuki, Ippei Shimoshikiryo, Sadao Suzuki, Takeshi Nishiyama, Miki Watanabe, Teruhide Koyama, Etsuko Ozaki, Isao Watanabe, Kiyonori Kuriki, Yoshikuni Kita, Hirotsugu Ueshima, Kenji Matsui, Kokichi Arisawa, Hirokazu Uemura, Sakurako Katsuura-Kamano, Sho Nakamura, Hiroto Narimatsu, Nobuyuki Hamajima, Hideo Tanaka, Kenji Wakai

Journal of epidemiology Vol. 31 ( 12 ) page： 660 - 668 2021.12

Language：English Publishing type：Research paper (scientific journal) Publisher：Japan Epidemiological Association

BACKGROUND: The Japan Multi-institutional Collaborative Cohort (J-MICC) study was launched in 2005 to examine gene-environment interactions in lifestyle-related diseases, including cancers, among the Japanese. This report describes the study design and baseline profile of the study participants. METHODS: The participants of the J-MICC Study were individuals aged 35 to 69 years enrolled from respondents to study announcements in specified regions, inhabitants attending health checkup examinations provided by local governments, visitors at health checkup centers, and first-visit patients at a cancer hospital in Japan. At the time of the baseline survey, from 2005 to 2014, we obtained comprehensive information regarding demographics, education, alcohol consumption, smoking, sleeping, exercise, food intake frequency, medication and supplement use, personal and family disease history, psychological stress, and female reproductive history, and collected peripheral blood samples. RESULTS: The baseline survey included 92,610 adults (mean age: 55.2 [9.4] years, 44.1% men) from 14 study regions in 12 prefectures. The participation rate was 33.5%, with participation ranging from 19.7% to 69.8% in different study regions. The largest number of participants was in the age groups of 65-69 years for men and 60-64 years for women. There were differences in body mass index, educational attainment, alcohol consumption, smoking, and sleep duration between men and women. CONCLUSIONS: The J-MICC Study collected lifestyle and clinical data and biospecimens from over 90,000 participants. This cohort is expected to be a valuable resource for the national and international scientific community in providing evidence to support longer healthy lives.

DOI： 10.2188/jea.JE20200147

The Relationship between Dental Findings and Tongue Pressure: A Survey of 745 Community-Dwelling Adults and Elderly Persons in Japan Invited Reviewed International journal

Kensuke Tashiro, Sakiko Soutome, Madoka Funahara, Yumiko Kawashita, Masayasu Kitamura, Hideki Fukuda, Reiko Furugen, Takahiro Iwasaki, Hideaki Hayashida, Koji Kawasaki, Miho Higashi, Mako Nagayoshi, Noboru Takamura, Takahiro Maeda, Toshiyuki Saito

Gerontology Vol. 67 ( 5 ) page： 517 - 524 2021.10

Language：English Publishing type：Research paper (scientific journal) Publisher：S. Karger AG

Introduction: Reduced tongue pressure is one of the causes of dysphagia. The purpose of this study was to investigate the relationship between dental findings and tongue pressure, and whether prosthetic treatment prevents reduced tongue pressure. Methods: This was a cross-sectional study. Participants were 745 community-dwelling adults and elderly persons in the Goto Islands in Nagasaki, who underwent a health checkup for residents in 2015 and 2016. Data were collected on gender; age; grip strength; hemoglobin; Creatinine (Cr); glycated hemoglobin (HbA1c); history of stroke; smoking, drinking, exercise, and walking habits; number of teeth; wearing of removable dentures; functional units of natural teeth (n-FTUs), fixed prostheses (nif-FTUs), and removable dentures (t-FTUs); and tongue pressure. The associations between each variable and tongue pressure were examined using multiple regression analysis. Next, those with 3 or fewer n-FTUs were selected, and differences in tongue pressure were compared between those with 3 or fewer nif-FTUs and those with 4 or more nif-FTUs, using a propensity score matching method. Results: Male gender, weak grip strength, low HbA1c, no drinking, and a low number of teeth were independent factors significantly associated with lower tongue pressure. Among participants with 3 or fewer n-FTUs, the 43 with 4 or more nif-FTUs showed significantly higher tongue pressure than the 43 with 3 or fewer nif-FTUs after propensity score matching, although the number of t-FTUs was not associated with tongue pressure. Discussion/Conclusion: Tooth loss was significantly associated with lower tongue pressure. It was suggested that fixed prosthesis treatment might prevent the reduction of tongue pressure, but removable dentures did not have such an effect.

DOI： 10.1159/000513599

Both variants of A1CF and BAZ1B genes are associated with gout susceptibility: a replication study and meta-analysis in a Japanese population Invited Reviewed

Makoto Kawaguchi, Akiyoshi Nakayama, Yuka Aoyagi, Takahiro Nakamura, Seiko Shimizu, Yusuke Kawamura, Mikiya Takao, Takashi Tamura, Asahi Hishida, Mako Nagayoshi, Mitsuo Nagase, Keiko Ooyama, Hiroshi Ooyama, Nariyoshi Shinomiya, Hirotaka Matsuo

Human Cell Vol. 34 ( 2 ) page： 293 - 299 2021.3

Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media LLC

<title>Abstract</title>Gout is a common type of acute arthritis that results from elevated serum uric acid (SUA) levels. Recent genome-wide association studies (GWASs) have revealed several novel single nucleotide polymorphism (SNPs) associated with SUA levels. Of these, rs10821905 of <italic>A1CF</italic> and rs1178977 of <italic>BAZ1B</italic> showed the greatest and the second greatest significant effect size for increasing SUA level in the Japanese population, but their association with gout is not clear. We examined their association with gout using 1411 clinically-defined Japanese gout patients and 1285 controls, and meta-analyzed our previous gout GWAS data to investigate any association with gout. Replication studies revealed both SNPs to be significantly associated with gout (<italic>P</italic> = 0.0366, odds ratio [OR] with 95% confidence interval [CI]: 1.30 [1.02–1.68] for rs10821905 of <italic>A1CF</italic>, <italic>P</italic> = 6.49 × 10<sup>–3</sup>, OR with 95% CI: 1.29 [1.07–1.55] for rs1178977 of <italic>BAZ1B</italic>). Meta-analysis also revealed a significant association with gout in both SNPs (<italic>P</italic><sub><italic>meta</italic></sub> = 3.16 × 10<sup>–4</sup>, OR with 95% CI: 1.39 [1.17–1.66] for rs10821905 of <italic>A1CF</italic>, <italic>P</italic><sub><italic>meta</italic></sub> = 7.28 × 10<sup>–5</sup>, OR with 95% CI 1.32 [1.15–1.51] for rs1178977 of <italic>BAZ1B</italic>). This study shows the first known association between SNPs of <italic>A1CF</italic>, <italic>BAZ1B</italic> and clinically-defined gout cases in Japanese. Our results also suggest a shared physiological/pathophysiological background between several populations, including Japanese, for both SUA increase and gout susceptibility. Our findings will not only assist the elucidation of the pathophysiology of gout and hyperuricemia, but also suggest new molecular targets.

DOI： 10.1007/s13577-021-00485-4

Other Link： http://link.springer.com/article/10.1007/s13577-021-00485-4/fulltext.html

The relationship between dental findings and tongue pressure: a survey of 745 community-dwelling adults and elderly persons in Japan Reviewed

Kensuke Tashiro, Sakiko Soutome, Madoka Funahara, Yumiko Kawashita, Masayasu Kitamura, Hideki Fukuda, Reiko Furugen, Takahiro Iwasaki, Hideaki Hayashida, Koji Kawasaki, Miho Higashi, Mako Nagayoshi, Noboru Takamura, Takahiro Maeda, Toshiyuki Saito

Gerontology Vol. 67 ( 4 ) page： 387 - 394 2021.2

Genome-wide association study of serum prostate-specific antigen levels based on 1000 Genomes imputed data in Japanese: the Japan Multi-Institutional Collaborative Cohort Study. Invited Reviewed

Asahi Hishida, Masahiro Nakatochi, Takashi Tamura, Mako Nagayoshi, Rieko Okada, Yoko Kubo, Mineko Tsukamoto, Yuka Kadomatsu, Sadao Suzuki, Takeshi Nishiyama, Nagato Kuriyama, Isao Watanabe, Toshiro Takezaki, Daisaku Nishimoto, Kiyonori Kuriki, Kokichi Arisawa, Sakurako Katsuura-Kamano, Haruo Mikami, Miho Kusakabe, Isao Oze, Yuriko N Koyanagi, Yasuyuki Nakamura, Aya Kadota, Chisato Shimanoe, Keitaro Tanaka, Hiroaki Ikezaki, Masayuki Murata, Michiaki Kubo, Yukihide Momozawa, Kenji Takeuchi, Kenji Wakai

Nagoya journal of medical science Vol. 83 ( 1 ) page： 183 - 194 2021.2

Language：English Publishing type：Research paper (scientific journal)

Prostate cancer is emerging as a significant global public health burden. The incidence and prevalence of prostate cancer has increased in Japan, as westernized lifestyles become more popular. Recent advances in genetic epidemiology, including genome-wide association studies (GWASs), have identified considerable numbers of human genetic factors associated with diseases. Several GWASs have reported significant loci associated with serum prostate-specific antigen (PSA) levels. One GWAS, which was based on classic GWAS microarray measurements, has been reported for Japanese so far. In the present study, we conducted a GWAS of serum PSA using 1000Genomes imputed GWAS data (n =1,216) from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study, to detect candidate novel genetic loci that influence serum PSA levels in Japanese. The association of SNPs/genetic variants with serum PSA as a continuous variable was tested using the linear Wald test. SNP rs10000006 in SGMS2 (sphingomyelin synthase 2) on chromosome 4 had genome-wide significance (P <5×10-8), and eight variants on three chromosomes (chromosomes 12, 14, 15) had genome-wide suggestive levels of significance (P <1×10-6). With an independent data set from the J-MICC Shizuoka Study (n = 2,447), the association of the SGMS2 SNP with blood PSA levels was not replicated. Although our GWAS failed to detect novel loci associated with serum PSA levels in the Japanese cohort, it confirmed the significant effects of previously reported genetic loci on PSA levels in Japanese. Importantly, our results confirmed the significance of KLK3 SNPs also in Japanese, implying that consideration of individual genetic information in prostate cancer diagnosis may be possible in the future.

DOI： 10.18999/nagjms.83.1.183

Sarcopenia is associated with insomnia in Japanese older adults: a cross-sectional study of data from the Nagasaki Islands study Invited Reviewed International journal

Yuki Nagaura, Hideaki Kondo, Mako Nagayoshi, Takahiro Maeda

BMC Geriatrics Vol. 20 ( 1 ) page： 256 - 256 2020.12

Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media LLC

<title>Abstract</title><sec>
<title>Background</title>
Sarcopenia is associated with increased mortality among older adults. Sleep-related problems have been studied as factors related to sarcopenia. This study was conducted to determine the relationship between sleep-related problems and sarcopenia among Japanese community-dwelling older adults using data from the Nagasaki Islands Study.

</sec><sec>
<title>Methods</title>
This cross-sectional study analyzed data collected from 2017 to 2018. A total of 1592 older adults (575 men, 36.1%) aged 65 years or older participated. Sarcopenia was evaluated using the skeletal muscle mass index and grasp powers based on the criteria of the Asian Working Group for Sarcopenia. Odds ratios for sarcopenia were calculated using logistic regression analysis. Furthermore, subgroup analysis was performed based on the following tertiles of age: 65–70 years, 71–78 years, and 79–98 years.

</sec><sec>
<title>Results</title>
The number of participants with sarcopenia was 238 (14.9%). The median age of participants in the sarcopenia group (80 years; interquartile range: 74–84) was significantly higher than in the non-sarcopenia group (73 years; interquartile range 69–79; <italic>P</italic> < 0.001). In the sarco<italic>p</italic>enia group, 70.9% of participants had difficulty initiating and/or maintaining sleep, sleep duration tended to be longer (<italic>P</italic> < 0.001), and 33.3% of participants’ sleep duration was over 9 h. In a logistic regression analysis for sarcopenia, advancing age was the most prominent factor, and the adjusted odds ratio (95% confidence interval) of facing difficulty initiating and/or maintaining sleep was 1.60 (1.14–2.25). Despite longer sleep duration being a significant factor in the univariable analysis, it was not significant in the multivariable analysis. In the logistic regression analysis for sarcopenia among older adults aged 79–98 years, the odds ratio (95% confidence interval) among women was significantly low at 0.53 (0.33–0.83).

</sec><sec>
<title>Conclusions</title>
Sarcopenia is associated with difficulty initiating and/or maintaining sleep among Japanese older adults. In sarcopenia control measures, sleep/wake disorders related to insomnia are required to be evaluated in detail to help inform nursing and medical policy.

</sec>

DOI： 10.1186/s12877-020-01658-w

Other Link： https://link.springer.com/article/10.1186/s12877-020-01658-w/fulltext.html

AB1232 ORAL DYSBIOSIS REFLECTS THE IMMUNOLOGICAL ALTERATION OF RA REGARDING TO ACPA AND HLA DRB1*SE: NAGASAKI ISLAND STUDY Reviewed

Y. Tsuji, M. Tamai, S. Morimoto, D. Sasaki, M. Nagayoshi, F. Nonaka, S. Y. Kawashiri, K. Yanagihara, T. Saito, K. Aoyagi, T. Maeda, F. Matsuda, A. Kawakami

Annals of the Rheumatic Diseases Vol. 79 ( Suppl 1 ) page： 1907.2 - 1907 2020.6

Language：English Publishing type：Research paper (scientific journal) Publisher：BMJ

<sec><title>Background:</title>Anti-citrullinated protein antibody (ACPA) production is observed in several organs even prior to the onset of rheumatoid arthritis (RA), and oral mucosa is considered to be one of the important tissues. The presence of HLA-DRB1*SE closely associates with ACPA production. Saliva is considered to reflect the oral microbiota including periodontal disease. Alteration of oral microbiota of RA becomes to be normalized by DMARDs treatment, however, the interaction of HLA-DRB1*SE, ACPA and oral microbiota of RA patients remains to be elucidated.

</sec><sec><title>Objectives:</title>The Nagasaki Island Study, which had started in 2014 collaborating with Goto City, is intended for research of the preclinical stage of RA, including ACPA/HLA genotype screening and ultrasound and magnetic resonance imaging examinations in high-risk subjects. Using the samples accumulated in this cohort, we have tried to investigate the difference of oral microbiota among RA patients and healthy subjects regarding to ACPA and HLA-DRB1*SE.

</sec><sec><title>Methods:</title>Blood and salivary samples were obtained from 1422 subjects out of 4276 who have participated in the Nagasaki Island Study from 2016 to 2018. ACPA positivity was 1.7 % in total. Some of RA patients resided in Goto City participated in the Nagasaki Island Study. At this point, we selected 291 subjects, who were ACPA positive non-RA healthy subjects (n=22) and patients with RA (n=33, 11 subjects were ACPA positive and 22 ACPA negative respectively) as the case, age and gender matched ACPA negative non-RA healthy subjects (n=236) as the control. ACPA was measured by an enzyme-linked immunosorbent assay, and HLA genotyping was quantified by next-generation sequencing (Ref.1). The operational taxonomic unit (OUT) analysis using 16S rRNA gene sequencing were performed. The richness of microbial diversity within-subject (alpha diversity) was scaled via Shannon entropy. The dissimilarity between microbial community composition was calculated using Bray-Curtis distance as a scale, and differences between groups (beta diversity) were tested by permutational multivariate analysis of variance (PERMANOVA). In addition, UniFrac distance calculated in consideration of the distance on the phylogenetic tree were performed.

</sec><sec><title>Results:</title>Median age 70 y.o., % Female 58.8 %. Among RA and non-RA subjects, not alpha diversity but beta diversity was statistically significance (p=0.022, small in RA). In RA subjects, both alpha and beta diversity is small (p<0.0001), especially significant in ACPA positive RA (Figure 1). Amongt RA subjects, presence of HLA-DRB1*SE did not show the difference but the tendency of being small of alpha diversity (p=0.29).

</sec><sec><title>Conclusion:</title>Our study has suggested for the first time the association of oral microbiota alteration with the presence of ACPA and HLA-DRB1*SE. Oral dysbiosis may reflect the immunological status of patients with RA.

</sec><sec><title>References:</title>[1]Kawaguchi S, et al. Methods Mol Biol 2018;1802: 22

</sec><sec><title>Disclosure of Interests:</title>None declared

</sec>

DOI： 10.1136/annrheumdis-2020-eular.5147

Cardio-ankle vascular index and circulating CD34-positive cell levels as indicators of endothelial repair activity in older Japanese men. Reviewed

Yuji Shimizu, Hirotomo Yamanashi, Yuko Noguchi, Jun Koyamatsu, Mako Nagayoshi, Kairi Kiyoura, Shoichi Fukui, Mami Tamai, Shin-Ya Kawashiri, Hideaki Kondo, Takahiro Maeda

Geriatrics & gerontology international Vol. 19 ( 6 ) page： 557 - 562 2019.6

Language：English Publishing type：Research paper (scientific journal)

AIM: The cardio-ankle vascular index (CAVI) reflects functional arterial stiffness, which is related to endothelial dysfunction. CD34-positive cells carry out an important function in endothelial repair. However, there have been no reports assessing the association between CAVI and the number of circulating CD34-positive cells. METHODS: We carried out a cross-sectional study of 249 Japanese men, aged 60-69 years, who underwent annual health checkups between 2013 and 2015. As individuals with high levels of circulating CD34-positive cells might indicate the influence of consumptive reduction of circulating CD34-positive cells as a result of aggressive endothelial repair, participants were stratified by circulating CD34-positive cell levels, using the median value in this population (0.95 cells/μL) as the cut-off. RESULTS: For participants with low circulating CD34-positive cell levels, logarithmic values of circulating CD34-positive cells were inversely associated with CAVI (multivariable standardized parameter estimate [β] = -0.22, P = 0.014), but not for participants with high levels (β = -0.04, P = 0.638). In addition, even when no significant associations between CAVI and carotid intima-media thickness were detected for participants with low circulating CD34-positive cell levels (β = -0.02, P = 0.865), significant positive associations were identified for participants with high levels (β = 0.22, P = 0.028). CONCLUSIONS: As circulating CD34-positive cell count might indicate endothelial repair activity, the present results show that CAVI is affected by insufficient endothelial repair in individuals with low circulating CD34-positive cell counts. Our results also show that a positive association between CAVI and carotid intima-media thickness exists only in individuals with aggressive endothelial repair, which indicates the presence of organic arterial disease, such as atherosclerosis. Geriatr Gerontol Int 2019; 19: 557-562.

DOI： 10.1111/ggi.13657

Short stature-related single-nucleotide polymorphism (SNP) activates endothelial repair activity in elderly Japanese. Reviewed International journal

Yuji Shimizu, Hirotomo Yamanashi, Yuko Noguchi, Jun Koyamatsu, Mako Nagayoshi, Kairi Kiyoura, Shoichi Fukui, Mami Tamai, Shin-Ya Kawashiri, Kazuhiko Arima, Takahiro Maeda

Environmental health and preventive medicine Vol. 24 ( 1 ) page： 26 - 26 2019.5

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Hypertension and atherosclerosis are bidirectionally related, while platelet count could serve as an indicator of endothelial repair. Therefore, high platelet counts could be associated with hypertension by indicating more intense endothelial repair activity. Furthermore, short stature has been shown to constitute a risk of atherosclerosis. Since inflammation-related single-nucleotide polymorphism (SNP (rs3782886)) is reportedly associated with myocardial infarction and short stature, rs3782886 could be associated with a high platelet count and thus more intense endothelial repair activity. METHODS: We conducted a cross-sectional study of 988 elderly Japanese who participated in a general health check-up. Short stature was defined as a height of at or under the 25th percentile of the study population, and high platelet count as the highest tertiles of the platelet levels. RESULTS: High platelet counts were found to be independently and positively associated with hypertension while rs3782886 was independently associated with high platelet levels and short stature. The classical cardiovascular risk factor-adjusted odds ratio (OR) and 95% confidence interval (CI) of high platelet count for hypertension was 1.34 (1.02, 1.77). With non-minor homo of the rs3782886 as the reference group, the adjusted OR and 95% CI for high platelet count and short stature of minor home were 2.40 (1.30, 4.42) and 2.21 (1.16, 4.21), respectively. CONCLUSION: SNP (rs3782886) was shown to be associated with high platelet count and short stature. This result partly explains how a genetic factor can influence the impact of height on endothelial repair.

DOI： 10.1186/s12199-019-0780-1

Association between chronic kidney disease and carotid intima-media thickness in relation to circulating CD34-positive cell count among community-dwelling elderly Japanese men. Reviewed International journal

Yuji Shimizu, Hirotomo Yamanashi, Yuko Noguchi, Jun Koyamatsu, Mako Nagayoshi, Kairi Kiyoura, Shoichi Fukui, Mami Tamai, Shin-Ya Kawashiri, Hideaki Kondo, Takahiro Maeda

Atherosclerosis Vol. 283 page： 85 - 91 2019.4

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND AND AIMS: Endothelial injury is well-known as a process that can lead to chronic kidney disease (CKD) and atherosclerosis. Hematopoietic activity is known to be associated inversely with CKD and positively with atherosclerosis. Since bone-derived progenitor cells (CD34-positive cells) contribute to endothelial repair (including the progression of atherosclerosis), understanding the association between CKD and carotid intima-media thickness (CIMT), in relation to circulating CD34-positive cell count, may be an efficient means of clarifying the mechanisms underlying endothelial activity. METHODS: We conducted a cross-sectional study of 570 elderly Japanese men aged 60-69 years, who underwent a general health check-up. Participants were stratified as per a median circulating CD34-positive cell count (1.01 cells/μL). RESULTS: Independent of the known cardiovascular risk factors, CIMT was found to be positively associated with CKD in the participants with high circulating CD34-positive cell counts but not in participants with low counts. Odds ratios were 1.40 (1.04, 1.89) for participants with high and 1.01 (0.72, 1.43) for participants with low circulating CD34-positive cell counts after adjustment for known cardiovascular risk factors at 95% confidence intervals for CKD with one standard deviation increment of CIMT. CONCLUSIONS: A positive association between CIMT and CKD was observed among participants with high circulating CD34-positive cell counts but not among participants with low counts. Endothelial repair activity might determine the association between CKD and CIMT.

DOI： 10.1016/j.atherosclerosis.2019.02.004

Association between height and circulating CD34-positive cells taken into account for the influence of enhanced production among elderly Japanese men: a cross-sectional study. Reviewed International journal

Yuji Shimizu, Hirotomo Yamanashi, Yuko Noguchi, Jun Koyamatsu, Mako Nagayoshi, Kairi Kiyoura, Shoichi Fukui, Mami Tamai, Shin-Ya Kawashiri, Kazuhiko Arima, Takahiro Maeda

Aging Vol. 11 ( 2 ) page： 663 - 672 2019.1

Language：English Publishing type：Research paper (scientific journal)

Recent studies have revealed an inverse association between height and cardiovascular disease and that endothelial progenitor cells (CD34-positive cells) contribute to vascular maintenance, which is associated with cardiovascular disease. However, evidence of the association between height and CD34-positive positive cells among elderly participants is limited. To assess this association, we conducted a cross-sectional study of 231 elderly Japanese men aged 65-69. Since enhanced production of circulating CD34-positive cells in response to endothelial injury might act have a strong confounding effect on the association between height and circulating CD34-positive cells, the median value for the levels of these cells (0.93 cells/μL) was used to stratify the participants. Multivariable linear regression analysis demonstrated that height was significantly positively associated with circulating CD34-positive cells for those participants with low levels of circulating CD34-positive cells (n=114) but not for those with higher levels (n=117), with a multi-adjusted standardized parameter estimate (β) of 0.27 (p=0.008) for low and 0.11 (0.275) for higher circulating CD34-positive cell levels. The positive association is limited to participants with relatively low circulating CD34-positive cell levels, whose productivity of these cells is not activated. Our findings indicate that height is an indicator of vascular maintenance capability in elderly Japanese men.

DOI： 10.18632/aging.101768

Association of hemoglobin concentration with handgrip strength in relation to hepatocyte growth factor levels among elderly Japanese men aged 60-69 years: a cross-sectional study. Reviewed International journal

Yuji Shimizu, Hirotomo Yamanashi, Yuko Noguchi, Jun Koyamatsu, Mako Nagayoshi, Kairi Kiyoura, Shoichi Fukui, Mami Tamai, Shin-Ya Kawashiri, Kazuhiko Arima, Takahiro Maeda

Environmental health and preventive medicine Vol. 23 ( 1 ) page： 56 - 56 2018.11

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Hemoglobin concentration reportedly is positively associated with muscle strength, for example, handgrip strength. However, hemoglobin cannot repair muscle directly, but is beneficial only in a supportive role. Since hepatocyte growth factor (HGF) regulates muscle satellite cell production and differentiation, which is stimulated by organ injury, the supportive effect of hemoglobin should thus be stronger for participants with high HGF than for those with low HGF. However, the association between hemoglobin concentration and handgrip strength in relation to HGF levels remains unknown. METHODS: We conducted a cross-sectional study of 255 Japanese elderly men aged 60-69 years who participated in annual health check-ups in 2014-2015. The study population was categorized on the basis of a median value of HGF of 300.6 pg/mL. RESULTS: Among present study population, 128 participants showed low HGF. For participants with low HGF, hemoglobin concentration showed no significant association with handgrip strength (standardized parameter estimate (β) = 0.03, p = 0.767), but for those with high HGF, hemoglobin concentration was significantly positively associated with handgrip strength (β = 0.23, p = 0.014). CONCLUSIONS: A significant positive association between hemoglobin level and handgrip strength was established for elderly Japanese men aged 60-69 years with high HGF but not for participants with low HGF. Our finding indicates that HGF levels could determine the relationship of hemoglobin concentration with handgrip strength in elderly Japanese men aged 60-69 years. This result can be expected to serve as an effective tool for the clarification of the roles played by HGF and hemoglobin concentration in maintenance of muscle strength.

DOI： 10.1186/s12199-018-0744-x

Sleep disorders among Yusho patients highly intoxicated with dioxin-related compounds: A 140-case series. Reviewed International journal

Hideaki Kondo, Keiko Tanio, Yuki Nagaura, Mako Nagayoshi, Chikage Mitoma, Masutaka Furue, Takahiro Maeda

Environmental research Vol. 166 page： 261 - 268 2018.10

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: Patients with Yusho, a condition caused by exposure to dioxins and dioxin-like compounds, have diverse mental and physical complaints. However, the relationship between dioxins and sleep disorders has not yet been examined. This cross-sectional study was designed to investigate problems associated with sleep among patients with Yusho. METHODS: A total of 140 participants (52.9% men, average age: 67.1 ± 12.2 years) were examined using questionnaires and medical interviews by an expert on sleep medicine. Demographic and clinical characteristics, including blood concentrations of 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), which is the major cause of Yusho, were obtained from the results of recent surveys conducted by the Yusho Study Group. RESULTS: Moderate to severe symptoms of insomnia were present in 51.8% of the patients. The median Pittsburgh Sleep Quality Index global score (PSQI GS) was 8 (interquartile range: 5-11). The prevalence of restless legs syndrome/Willis-Ekbom disease (RLS/WED) was 30.7%; 24.3% of patients had severe RLS/WED (distressing symptoms with a frequency ≥ 1day per week). A higher blood concentration of 2,3,4,7,8-PeCDF (≥72.27 pg/g lipid) and severe RLS/WED were associated with higher odds of a PSQI GS ≥8, after adjusting for covariates (odds ratio [95% confidence interval]: 4.84 [1.10-21.25] and 4.15 [1.53-11.28], respectively). CONCLUSIONS: Symptoms of insomnia were frequent, and the prevalence of RLS/WED was high in patients with Yusho. In addition to the presence of RLS/WED, a higher blood concentration of 2,3,4,7,8-PeCDF was associated with lower subjective sleep quality.

DOI： 10.1016/j.envres.2018.05.033

Single nucleotide polymorphism as an indicator of short stature and dyslipidemia in community-dwelling elderly Japanese subjects

Tezuka, Kazuhide, Shimizu, Yuji, Noguchi, Yuko, Sato, Shimpei, Koyamatsu, Jun, Yamanashi, Hirotomo, Nagayoshi, Mako, Kawashiri, Shin-Ya, Nagata, Yasuhiro, Maeda, Takahiro

Acta Medica Nagasakiensia Vol. 62 ( 1 ) page： 7 - 14 2018.10

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