No strong association among epigenetic modifications by DNA methylation, telomere length, and physical fitness in biological aging.

Cellular senescence is greatly accelerated by telomere shortening, and the steps forward in human aging are strongly influenced by environmental and lifestyle factors, whether DNA methylation (DNAm) is affected by exercise training, remains unclear. In the present study, we investigated the relationships between physiological functions, maximal oxygen uptake (VO2max), vertical jump, working memory, telomere length (TL) assessed by RT-PCR, DNA methylation-based estimation of TL (DNAmTL), and DNA methylation-based biomarkers of aging of master rowers (N = 146) and sedentary subjects (N = 95), aged between 37 and 85 years. It was found that the TL inversely correlated with chronological age. We could not detect an association between telomere length and VO2max, vertical jump, and working memory by RT-PCR method, while these physiological test results showed a correlation with DNAmTL. DNAmGrimAge and DNAmPhenoAge acceleration were inversely associated with telomere length assessed by both methods. It appears that there are no strong beneficial effects of exercise or physiological fitness on telomere shortening, however, the degree of DNA methylation is associated with telomere length.

Coffee consumption and skeletal muscle mass: WASEDA'S Health Study.

Few studies have examined the association between coffee consumption and muscle mass; their results are conflicting. Therefore, we examined the association between coffee consumption and low muscle mass prevalence. We also performed an exploratory investigation of the potential effect modification by demographic, health status-related and physical activity-related covariates. This cross-sectional study included 2085 adults aged 40-87 years. The frequency of coffee consumption was assessed using a self-administered questionnaire. Muscle mass was assessed as appendicular skeletal muscle mass/height2 using a multifrequency bioelectrical impedance analyser. We defined low muscle mass using cut-offs recommended by the Asian Working Group for Sarcopenia. Multivariable-adjusted OR for low muscle mass prevalence were estimated using a logistic regression model. The prevalence of low muscle mass was 5·4 % (n 113). Compared with the lowest coffee consumption group (< 1 cup/week), the multivariable-adjusted OR (95 % CI) of low muscle mass prevalence were 0·62 (0·30, 1·29) for 1-3 cups/week, 0·53 (0·29, 0·96) for 4-6 cups/week or 1 cup/d and 0·28 (0·15, 0·53) for ≥ 2 cups/d (P for trend < 0·001). There were no significant interactions among the various covariates after Bonferroni correction. In conclusion, coffee consumption may be inversely associated with low muscle mass prevalence.

The MMAAS Project: An Observational Human Study Investigating the Effect of Anabolic Androgenic Steroid Use on Gene Expression and the Molecular Mechanism of Muscle Memory.

OBJECTIVE: It remains unknown whether myonuclei remain elevated post anabolic-androgenic steroid (AAS) usage in humans. Limited data exist on AAS-induced changes in gene expression. DESIGN: Cross-sectional/longitudinal. SETTING: University. PARTICIPANTS: Fifty-six men aged 20 to 42 years. INDEPENDENT VARIABLES: Non-resistance-trained (C) or resistance-trained (RT), RT currently using AAS (RT-AS), of which if AAS usage ceased for ≥18 weeks resampled as Returning Participants (RP) or RT previously using AAS (PREV). MAIN OUTCOME MEASURES: Myonuclei per fiber and cross-sectional area (CSA) of trapezius muscle fibers. RESULTS: There were no significant differences between C (n = 5), RT (n = 15), RT-AS (n = 17), and PREV (n = 6) for myonuclei per fiber. Three of 5 returning participants (RP1-3) were biopsied twice. Before visit 1, RP1 ceased AAS usage 34 weeks before, RP2 and RP3 ceased AAS usage ≤2 weeks before, and all had 28 weeks between visits. Fiber CSA decreased for RP1 and RP2 between visits (7566 vs 6629 µm 2 ; 7854 vs 5677 µm 2 ) while myonuclei per fiber remained similar (3.5 vs 3.4; 2.5 vs 2.6). Respectively, these values increased for RP3 between visits (7167 vs 7889 µm 2 ; 2.6 vs 3.3). CONCLUSIONS: This cohort of past AAS users did not have elevated myonuclei per fiber values, unlike previous research, but reported AAS usage was much lower. Training and AAS usage history also varied widely among participants. Comparable myonuclei per fiber numbers despite decrements in fiber CSA postexposure adheres with the muscle memory mechanism, but there is variation in usage relative to sampling date and low numbers of returning participants.

Association between alcohol dietary pattern and prevalence of dyslipidaemia: WASEDA'S Health Study.

The association between a dietary pattern characterised by high alcohol intake and dyslipidaemia has not been fully investigated. Therefore, the present study aimed to investigate the association between alcohol dietary patterns and the prevalence of dyslipidaemia and its components. This cross-sectional study enrolled 2171 men and women aged ≥40 years who were alumni of a Japanese university. To identify dietary patterns, a principal component analysis was performed based on the energy-adjusted food intake estimated by a brief-type self-administered diet history questionnaire. Three dietary patterns were identified, the second of which was named the alcohol dietary pattern and was characterised by a high intake of alcoholic beverages, liver, chicken and fish. This alcohol dietary pattern was associated with reduced LDL-cholesterol levels. The fully adjusted OR (95 % CI) of high LDL-cholesterol for the lowest through highest quartile of alcohol dietary pattern score were 1·00 (reference), 0·83 (0·64, 1·08), 0·84 (0·64, 1·10) and 0·68 (0·49, 0·94), respectively. Subgroup analysis showed that the alcohol dietary pattern was inversely associated with the prevalence of dyslipidaemia in women, whereas it was positively associated with high TAG levels in men. In conclusion, the alcohol dietary pattern, characterised by a high intake of alcoholic beverages, liver, chicken and fish, was associated with the prevalence of dyslipidaemia and its components. This finding provides useful information for the prevention and treatment of dyslipidaemia by modifying the diet.

The combination of cardiorespiratory fitness and muscular fitness, and prevalence of diabetes mellitus in middle-aged and older men: WASEDA'S Health Study.

BACKGROUND: Although the negative relationship between cardiorespiratory fitness (CRF) or muscular fitness and diabetes mellitus were respectively observed in many previous studies, there is still a lack of studies that include CRF and muscular fitness simultaneously. Therefore, this study aimed to investigate the relationship between the combination of CRF and muscular fitness and diabetes through a cross-sectional study.  METHODS: This study was part of WASEDA'S Health Study, a cohort study launched in 2014. We used a part of the baseline data collected for this study. Maximal exercise test using a cycle ergometer and leg extension power (LEP) test were respectively used to evaluate CRF and muscular fitness. Since LEP is affected by body weight, relative LEP (rLEP) which is LEP per body weight, was used as an index of muscular fitness. 796 men (56.5 ± 10.4 years old) who completed a medical examination and fitness tests, were divided into two groups based on CRF and rLEP, respectively. The prevalence of diabetes was collected based on a self-reported questionnaire or blood test. Odds ratios and 95% confidence intervals (CIs) for the prevalence of diabetes were obtained using logistic regression models while adjusting for age, body mass index, exercise habits, family history of diabetes, smoking habits, and drinking habits. RESULTS: 55 (7%) participants had diabetes. Compared to participants with lower CRF or rLEP, the odds ratio (95% CIs) of diabetes in those with higher CRF or rLEP was 0.46 (0.21-0.98) or 0.34 (0.16-0.74), respectively. Furthermore, using the lower CRF and lower rLEP group as the reference, the odds ratio (95% CIs) for the lower CRF and higher rLEP group was 0.32 (0.12-0.88), and higher CRF and higher rLEP group was 0.21 (0.07-0.63), after adjusting for potential confounding factors. CONCLUSIONS: CRF and rLEP have independent and joint inverse associations with diabetes prevalence. In addition, participants with high CRF and high rLEP had a lower prevalence of diabetes compared to those with only high CRF or only high rLEP.

Stool pattern is associated with not only the prevalence of tumorigenic bacteria isolated from fecal matter but also plasma and fecal fatty acids in healthy Japanese adults.

BACKGROUND: Colibactin-producing Escherichia coli containing polyketide synthase (pks+ E. coli) has been shown to be involved in colorectal cancer (CRC) development through gut microbiota analysis in animal models. Stool status has been associated with potentially adverse gut microbiome profiles from fecal analysis in adults. We examined the association between stool patterns and the prevalence of pks+ E. coli isolated from microbiota in fecal samples of 224 healthy Japanese individuals. RESULTS: Stool patterns were determined through factorial analysis using a previously validated questionnaire that included stool frequency, volume, color, shape, and odor. Factor scores were classified into tertiles. The prevalence of pks+ E. coli was determined by using specific primers for pks+ E. coli in fecal samples. Plasma and fecal fatty acids were measured via gas chromatography-mass spectrometry. The prevalence of pks+ E. coli was 26.8%. Three stool patterns identified by factorial analysis accounted for 70.1% of all patterns seen (factor 1: lower frequency, darker color, and harder shape; factor 2: higher volume and softer shape; and factor 3: darker color and stronger odor). Multivariable-adjusted odds ratios (95% confidence intervals) of the prevalence of pks+ E. coli for the highest versus the lowest third of the factor 1 score was 3.16 (1.38 to 7.24; P for trend = 0.006). This stool pattern exhibited a significant positive correlation with fecal isobutyrate, isovalerate, valerate, and hexanoate but showed a significant negative correlation with plasma eicosenoic acid and α-linoleic acid, as well as fecal propionate and succinate. No other stool patterns were significant. CONCLUSIONS: These results suggest that stool patterns may be useful in the evaluation of the presence of tumorigenic bacteria and fecal fatty acids through self-monitoring of stool status without the requirement for specialist technology or skill. Furthermore, it may provide valuable insight about effective strategies for the early discovery of CRC.

Comprehensive analysis of gut microbiota of a healthy population and covariates affecting microbial variation in two large Japanese cohorts.

BACKGROUND: Inter-individual variations in gut microbiota composition are observed even among healthy populations. The gut microbiota may exhibit a unique composition depending on the country of origin and race of individuals. To comprehensively understand the link between healthy gut microbiota and host state, it is beneficial to conduct large-scale cohort studies. The aim of the present study was to elucidate the integrated and non-redundant factors associated with gut microbiota composition within the Japanese population by 16S rRNA sequencing of fecal samples and questionnaire-based covariate analysis. RESULTS: A total of 1596 healthy Japanese individuals participated in this study via two independent cohorts, NIBIOHN cohort (n = 954) and MORINAGA cohort (n = 642). Gut microbiota composition was described and the interaction of these microorganisms with metadata parameters such as anthropometric measurements, bowel habits, medical history, and lifestyle were obtained. Thirteen genera, including Alistipes, Anaerostipes, Bacteroides, Bifidobacterium, Blautia, Eubacterium halli group, Faecalibacterium, Fusicatenibacter, Lachnoclostridium, Parabacteroides, Prevotella_9, Roseburia, and Subdoligranulum were predominant among the two cohorts. On the basis of univariate analysis for overall microbiome variation, 18 matching variables exhibited significant association in both cohorts. A stepwise redundancy analysis revealed that there were four common covariates, Bristol Stool Scale (BSS) scores, gender, age, and defecation frequency, displaying non-redundant association with gut microbial variance. CONCLUSIONS: We conducted a comprehensive analysis of gut microbiota in healthy Japanese individuals, based on two independent cohorts, and obtained reliable evidence that questionnaire-based covariates such as frequency of bowel movement and specific dietary habit affects the microbial composition of the gut. To our knowledge, this was the first study to investigate integrated and non-redundant factors associated with gut microbiota among Japanese populations.

Sport and exercise genomics: the FIMS 2019 consensus statement update.

Rapid advances in technologies in the field of genomics such as high throughput DNA sequencing, big data processing by machine learning algorithms and gene-editing techniques are expected to make precision medicine and gene-therapy a greater reality. However, this development will raise many important new issues, including ethical, moral, social and privacy issues. The field of exercise genomics has also advanced by incorporating these innovative technologies. There is therefore an urgent need for guiding references for sport and exercise genomics to allow the necessary advancements in this field of sport and exercise medicine, while protecting athletes from any invasion of privacy and misuse of their genomic information. Here, we update a previous consensus and develop a guiding reference for sport and exercise genomics based on a SWOT (Strengths, Weaknesses, Opportunities and Threats) analysis. This SWOT analysis and the developed guiding reference highlight the need for scientists/clinicians to be well-versed in ethics and data protection policy to advance sport and exercise genomics without compromising the privacy of athletes and the efforts of international sports federations. Conducting research based on the present guiding reference will mitigate to a great extent the risks brought about by inappropriate use of genomic information and allow further development of sport and exercise genomics in accordance with best ethical standards and international data protection principles and policies. This guiding reference should regularly be updated on the basis of new information emerging from the area of sport and exercise medicine as well as from the developments and challenges in genomics of health and disease in general in order to best protect the athletes, patients and all other relevant stakeholders.

Effect of Vitamin D Supplementation on Body Composition and Physical Fitness in Healthy Adults: A Double-Blind, Randomized Controlled Trial.

INTRODUCTION: This study aimed to clarify whether 1 year of vitamin D3 supplementation has a direct effect on body composition and physical fitness in healthy adults. METHODS: Ninety-five participants randomly received either 420 IU vitamin D3 per day (n = 48) or placebo (n = 47) in a double-blind manner for 1 year. Lean body mass and percentage body fat were determined. Physical fitness including hand grip strength, leg extension power and cardiorespiratory fitness (CRF) were assessed. Serum 25-hydroxyvitamin D (25[OH]D) and 1,25-dihydroxyvitamin D (1,25[OH]2D) concentrations were assessed using ELISA kits. RESULTS: Serum 25(OH)D and (1,25[OH]2D) concentrations significantly increased by approximately 11.2 ± 9.2 ng/mL (pinteraction <0.001)and 7.0 ± 7.8 pg/mL (pinteraction <0.001) after 1 year of vitamin D3 supplementation respectively. Lean body mass significantly increased from 43.8 ± 9.6 to 44.3 ± 9.8 kg in vitamin D group, while no change was observed in placebo group (from 42.6 ± 8.9 to 42.4± 8.9 kg) after 1 year intervention. Furthermore, no treatment effects on other indicators of body composition and physical fitness were observed. CONCLUSIONS: One year of vitamin D supplementation effectively improves lean body mass, but not muscle strength and CRF in healthy adults.

Association of Serum 25-Hydroxyvitamin D Concentrations With Glucose Profiles in Male Collegiate Football Athletes.

Low serum 25-hydroxyvitamin D [25(OH)D] concentrations are associated with a high risk of insulin resistance and Type 2 diabetes mellitus in adults. However, it is unknown whether this is the case for American collegiate football and rugby football athletes. This study investigated the associations between serum 25(OH)D concentrations and glucose profiles in male collegiate football athletes. Thirty-four collegiate athletes (13 American football players and 21 rugby football players) aged 21 years were recruited. Their body fat percent and visceral fat area were measured by dual-energy X-ray absorptiometry and magnetic resonance imaging, respectively. The participants completed an oral glucose tolerance test (75 g glucose) with venous blood samples obtained at time points 0, 30, 60, 90, and 120 min for the determination of plasma glucose and serum insulin concentrations. Fasting serum 25(OH)D concentrations were also measured. The prevalence of vitamin D deficiency and insufficiency was 17.6% and 58.8%, respectively. The serum 25(OH)D concentrations were negatively associated with the increments in the areas under the curve (iAUC) for glucose (r = -.429, p = .011) and were borderline significantly correlated with the Matsuda index (r = -.303, p = .082). No relationships were observed between the serum 25(OH)D concentrations and other glucose profiles. Multiple stepwise regression analysis of glucose iAUC concentrations as the dependent variable indicated that the serum 25(OH)D concentrations, but not body fat indicators, were independently associated with glucose iAUC (ß = -0.390, p = .025). The serum 25(OH)D concentrations were only an independent predictor for glucose iAUC in male collegiate football athletes, suggesting that increased 25(OH)D concentrations would be helpful for maintaining glucose homeostasis.

Ageing affects the association between serum 25- hydroxyvitamin D concentrations and cardiorespiratory fitness in middle-aged and elderly men.

BACKGROUND AND OBJECTIVES: The studies investigated the association between serum 25-hydroxyvitamin D (25(OH)D) concentrations and cardiorespiratory fitness (CRF) are few, and the results are controversial. We aim to evaluate the association of serum 25(OH)D concentrations with CRF in adults, and assess whether the associations vary with ageing. METHODS AND STUDY DESIGN: The study included 78 middle-aged (30-64 years) and 83 elderly (65-79 years) Japanese men. Hand grip strength and leg extension power were measured using hand grip and leg dynamometers, respectively. CRF was measured via a maximal graded exercise test and quantified as the peak oxygen uptake (VO2peak). Fasting serum 25(OH)D concentrations were determined by enzyme-linked immunosorbant assay. RESULTS: Serum 25(OH)D concentrations were positively related to hand grip strength (r=0.331, p<0.001), leg extension power (r=0.353, p<0.001), CRF (r=0.285, p<0.001) in all adults after adjustment for age. Significant interaction between 25(OH)D and age on CRF was observed (p<0.05). Age-related reduction of CRF was prevented in high 25(OH)D group (p<0.05). In the elderly, subjects in high 25(OH)D group had higher CRF compared with those in low group (p<0.05). CONCLUSIONS: We found that serum 25(OH)D concentrations significantly related with leg extension power, hand grip strength and CRF after adjustment for age. The relationship of vitamin D and CRF was affected by ageing. Higher serum 25(OH)D concentrations are a key predictor for CRF in the elderly, but not in middle-aged men.

Altitude Training and Recombinant Human Erythropoietin: Considerations for Doping Detection.

The benefit of training at altitude to enhance exercise performance remains equivocal although the most widely accepted approach is one where the athletes live and perform lower-intensity running at approximately 2300 m with high-intensity training at approximately 1250 m. The idea is that this method maintains maximal augmentations in total hemoglobin mass while reducing the performance impairment of high-intensity sessions performed at moderate altitude and thus preventing any detraining that can occur when athletes live and train at moderate altitude. This training regimen, however, is not universally accepted and some argue that the performance enhancement is due to placebo and training camp effects. Altitude training may affect an athlete's hematological parameters in ways similar to those observed following blood doping. Current methods of detection appear insufficient to differentiate between altitude training and blood doping making the interpretation of an athlete's biological passport difficult. Further research is required to determine the optimal method for altitude training and to enhance current detection methods to be able to differentiate better blood doping and altitude exposure.

Acute endurance exercise lowers serum fibroblast growth factor 21 levels in Japanese men.

OBJECTIVE: The independent effects of acute endurance exercise on FGF21 metabolism are poorly understood. Therefore, the purpose of this study was to determine whether acute endurance exercise modulates serum postprandial FGF21 levels in an age-dependent manner. DESIGN: Exercise intervention trial. PATIENTS: Twenty-eight subjects participated in the experiment, of whom 13 were excluded mainly because of a serum FGF21 level below the limit of detection. Thus, data from seven young (age: 18-22 years) and eight elderly male subjects (age: 62-69 years) were analysed. MEASUREMENTS: Participants were asked to perform a cycling exercise for 30 min at 70% maximal oxygen uptake, following carbohydrate intake. Blood samples were collected pre-exercise and 0 min, 30 min, 1 h, 3 h and 24 h after the cessation of exercise. Serum FGF21 levels were measured by an enzyme-linked immunosorbent assay. RESULTS: Higher serum FGF21 was observed in the elderly subjects group throughout the experiment (P < 0·05). There was no significant increase in serum FGF21 levels after the cessation of exercise, whereas serum FGF21 levels were significantly lower 24 h after the exercise compared with those pre-exercise, 0 min, 30 min and 1 h after the cessation of exercise in both groups (P < 0·01). The response did not differ between the two groups because of no significant group × time interaction. CONCLUSIONS: Acute endurance exercise lowers serum FGF21 levels 24 h following exercise. The results suggest that acute endurance exercise modulates postprandial FGF21 metabolism regardless of age.

Genetic risk score based on the lifetime prevalence of femoral fracture in 924 consecutive autopsies of Japanese males.

A genetic risk score (GRS) was developed for predicting fracture risk based on lifetime prevalence of femoral fractures in 924 consecutive autopsies of Japanese males. A total of 922 non-synonymous single nucleotide polymorphisms (SNPs) located in 62 osteoporosis susceptibility genes were genotyped and evaluated for their association with the prevalence of femoral fracture in autopsy cases. GRS values were calculated as the sum of risk allele counts (unweighted GRS) or the sum of weighted scores estimated from logistic regression coefficients (weighted GRS). Five SNPs (α-ʟ-iduronidase rs3755955, C7orf58 rs190543052, homeobox C4 rs75256744, G patch domain-containing gene 1 rs2287679, and Werner syndrome rs2230009) showed a significant association (P < 0.05) with the prevalence of femoral fracture in 924 male subjects. Both the unweighted and weighted GRS adequately predicted fracture prevalence; areas under receiver-operating characteristic curves were 0.750 [95 % confidence interval (CI) 0.660-0.840] and 0.770 (95 % CI 0.681-0.859), respectively. Multiple logistic regression analysis revealed that the odds ratio (OR) for the association between fracture prevalence and unweighted GRS ≥3 (n = 124) was 8.39 (95 % CI 4.22-16.69, P < 0.001) relative to a score <3 (n = 797). Likewise, the OR for a weighted GRS of 6-15 (n = 135) was 7.73 (95 % CI 3.89-15.36, P < 0.001) relative to scores of 0-5 (n = 786). The GRS based on risk allele profiles of the five SNPs could help identify at-risk individuals and enable implementation of preventive measures for femoral fracture.

Dietary patterns and nutritional assessment in middle-aged and elderly men.

Objectives Dietary patterns are studied to determine the relationship between diet and health. However, little is known about whether various dietary patterns fulfill adequate nutrient intake. Therefore, the purpose of this study was to investigate the association between major dietary patterns and nutritional intakes in middle-aged and elderly men. Furthermore, we examined the associations between dietary patterns and micronutrients status by using the reference values from the Dietary Reference Intakes for Japanese 2010 (DRIs-J 2010).Methods A total of 229 middle-aged and elderly men (age range, 40-79 years) participated in this study. The dietary patterns were determined using principal component analysis of 52 food and beverage items via a validated brief diet history questionnaire. Overall, micronutrient intake status was quantified using a dietary reference intakes score (DRIs-score) for 21 micronutrients (based on the DRIs-J 2010). The association of the nutrient intake and the DRIs-score with each factor score was evaluated using Spearman's correlation coefficient.Results Three dietary patterns were identified: "side dish", "evening drink", and "snack". The "side dish" pattern was characterized by a high intake of vegetables, fruits, seaweeds, mushrooms, and potatoes, and low intake of rice. Spearman's correlation showed that the "side dish" pattern correlated with each of the 21 micronutrients, and positively correlated with the DRIs-score (ρ=0.782, P<0.001).Conclusions The "side dish" pattern was positively related with the DRIs-score, calculated from the DRIs-J 2010. The result suggested the "side dish" pattern may provide a favorable nutrient balance in middle-aged and elderly men.

Polygenic risk for hypertriglyceridemia is attenuated in Japanese men with high fitness levels.

High cardiorespiratory fitness (CRF) is associated with a reduced risk for dyslipidemia; however, blood lipid levels are also affected by individual genetic variations. We performed a cross-sectional study to determine whether CRF modifies polygenic risk for dyslipidemia. Serum levels of triglycerides (TG), LDL cholesterol (LDL-C), and HDL cholesterol (HDL-C) were measured in 170 Japanese men (age 20-79 yr). CRF was assessed by measuring maximal oxygen uptake (Vo2max), and subjects were divided into low-fitness and high-fitness groups according to the reference Vo2max value for health promotion in Japan. We analyzed 19 single nucleotide polymorphisms (SNPs) associated with TG, LDL-C, or HDL-C levels. Based on these SNPs, we calculated three genetic risk scores (GRSs: TG-GRS, LDL-GRS, and HDL-GRS), and subjects were divided into low, middle, and high groups according to the tertile for each GRS. Serum TG levels of low-fitness individuals were higher in the high and middle TG-GRS groups than in the low TG-GRS group (P < 0.01 and P < 0.05, respectively), whereas no differences were detected in the TG levels of high-fitness individuals among the TG-GRS groups. In contrast, the high LDL-GRS group had higher LDL-C levels than did the low LDL-GRS group, and HDL-C levels were lower in the high HDL-GRS group than in the low HDL-GRS group regardless of the fitness level (P < 0.05). These results suggest that high CRF attenuates polygenic risk for hypertriglyceridemia; however, high CRF may not modify the polygenic risk associated with high LDL-C and low HDL-C levels in Japanese men.

High cardiorespiratory fitness can reduce glycated hemoglobin levels regardless of polygenic risk for Type 2 diabetes mellitus in nondiabetic Japanese men.

High cardiorespiratory fitness (CRF) is associated with a reduced risk of Type 2 diabetes mellitus (T2DM) and improved ß-cell function; genetic factors also determine these risks. This cross-sectional study investigated whether CRF modifies the association of polygenic risk of T2DM with glucose metabolism in nondiabetic Japanese men. Fasting plasma glucose, insulin, and glycated hemoglobin (HbA1c) levels were measured in 174 Japanese men (age: 20-79 yr). ß-Cell function and insulin resistance were evaluated by calculating HOMA-ß and HOMA-IR, respectively. CRF was assessed by measuring maximal oxygen uptake (V̇o2max). Subjects were divided into the low and high CRF groups within each age group according to the median V̇o2max. Eleven single nucleotide polymorphisms (SNPs) associated with T2DM were analyzed and used to calculate genetic risk score (GRS); subjects were divided into the low, middle, and high GRS groups. The high GRS group had higher HbA1c levels than the low GRS group in both the low and high CRF groups (P < 0.05). Furthermore, the individuals with a high GRS had a lower HOMA-ß than those with a low GRS regardless of CRF (P < 0.05). In multiple linear regression analysis, although GRS was a significant predictor of HbA1c (ß = 0.153, P = 0.025), V̇o2max was also associated with HbA1c (ß = -0.240, P = 0.041) independent of GRS. These results suggest that CRF is associated with HbA1c levels independent of GRS derived from T2DM-related SNPs; however, it does not modify the association of GRS with increased HbA1c or impaired ß-cell function.

Polygenic Risk Score, Cardiorespiratory Fitness, and Cardiometabolic Risk Factors: WASEDA'S Health Study.

PURPOSE: This study estimated an individual's genetic liability to cardiometabolic risk factors by polygenic risk score (PRS) construction and examined whether high cardiorespiratory fitness (CRF) modifies the association between PRS and cardiometabolic risk factors. METHODS: This cross-sectional study enrolled 1,296 Japanese adults aged ≥40 years. The PRS for each cardiometabolic trait (blood lipids, glucose, hypertension, and obesity) was calculated using the LDpred2 and clumping and thresholding methods. Participants were divided into low-, intermediate-, and high-PRS groups according to PRS tertiles for each trait. CRF was quantified as peak oxygen uptake (VO 2 peak) per kg body weight. Participants were divided into low-, intermediate-, and high-CRF groups according to the tertile VO 2 peak value. RESULTS: Linear regression analysis revealed a significant interaction between PRS for triglyceride (PRS TG ) and CRF groups on serum TG levels regardless of the PRS calculation method, and attenuated the association between PRS TG and TG levels in the high-CRF group. Logistic regression analysis revealed a significant sub-additive interaction between LDpred2 PRS TG and CRF on the prevalence of high TG, indicating that high CRF attenuated the genetic predisposition to high TG. Furthermore, a significant sub-additive interaction between PRS for body mass index and CRF on obesity was detected regardless of the PRS calculation method. These significant interaction effects on high TG and obesity were diminished in the sensitivity analysis using VO 2 peak per kg fat-free mass as the CRF index. Effects of PRSs for other cardiometabolic traits were not significantly attenuated in the high-CRF group regardless of PRS calculation methods. CONCLUSIONS: The findings of the present study suggest that individuals with high CRF overcome the genetic predisposition to high TG levels and obesity.