Japan Multi-Institutional Collaborative Cohort Research Articles

Relationship between Dietary Habits and Plasma Homocysteine Concentrations in Elderly Japanese Women and Men

The plasma homocysteine concentration is a good indicator of various diseases such as cardiovascular disease, stroke, and dementia. This study examined the relationship between plasma homocysteine concentrations and dietary habits in a population of elderly Japanese people from the Amami Islands. Data from 1131 participants collected during a baseline survey for the Japan Multi-institutional Collaborative Cohort study, which is a prospective cohort study, were used. Information on dietary habits was collected using a food frequency questionnaire. The plasma homocysteine concentration was associated with age in women only. Smoking in men and menopause were significantly associated with homocysteine concentrations. Analysis of blood biochemical data showed that estimate of glomerular filtration rate negatively correlated with plasma homocysteine in women (R = ?0.91, p < 0.001) and men (R = ?0.49, p < 0.001). There was no common food associated with homocysteine concentrations among the groups, but in each group, some food types were associated with homocysteine concentrations. In men, Chinese tea was a common factor showing a negative correlation with homocysteine concentrations. Natto showed a negative correlation with homocysteine concentrations in non-smoking men (β = ?0.11, p < 0.05) and premenopausal women (β = ?0.20, p < 0.01). Eggs (β = ?0.21, p < 0.01) and food processed from fish eggs (β = ?0.21, p < 0.01) negatively correlated with homocysteine concentrations in smoking men. Miso soup (β = ?0.13, p < 0.01) and yoghurt (β = ?0.10, p < 0.05) negatively correlated with homocysteine concentrations in postmenopausal women. Consumption of folate-rich food did not necessarily correlate with a low plasma Hcy concentration.

Nutrient-Derived Dietary Patterns and Their Association With Metabolic Syndrome in a Japanese Population

BackgroundNutrients have been proposed to be related to metabolic syndrome (MetS). The aims of this study were to identify dietary patterns that correlated with several nutrients using reduced rank regression (RRR) and to examine the association between extracted dietary patterns and prevalence of MetS in a Japanese population.MethodsThe study population comprised 1,092 Japanese men and women (35–69 years old) who had participated in the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study in Tokushima Prefecture. Dietary patterns were derived with RRR using 46 food items as predictors and six established nutrients (potassium, calcium, vitamin D, vitamin C, insoluble dietary fiber, and carotene) as response variables. Associations between extracted dietary patterns and MetS were then examined with logistic regression models.ResultsAmong the six dietary patterns, dietary pattern 1 (DP1) explained the largest proportion (60.1%) of variance in the six nutrients. Therefore, only DP1 was selected for further analysis. DP1 was characterized by high intake frequency of vegetables, fruits, fish and small fish, natto (fermented soybeans), and deep-fried tofu. After adjustment for potential confounders, significant inverse associations were found between DP1 score and MetS (odds ratio [OR] for each quartile: 1.00, 0.58, 0.60, 0.52; Ptrend = 0.02); DP1 and high blood pressure (Ptrend = 0.0002); and DP1 and high blood glucose (Ptrend = 0.02).ConclusionA dietary pattern characterized by high intake of vegetables, fruits, fish and small fish, natto, and deep-fried tofu was associated with reduced prevalence of MetS in a Japanese population.

Dietary calcium intake is associated with serum high-sensitivity C-reactive protein level in the general Japanese population.

The beneficial effects of dietary calcium intake on high-sensitivity C-reactive protein levels, a risk factor of cardiovascular disease, have not been fully elucidated. This study investigated the associations between dietary calcium intake and serum high-sensitivity C-reactive protein levels in the general Japanese population. We analyzed the data of 2,019 subjects (1,194 men and 825 women) aged 35 to 69 years in a cross-sectional study of the Japan Multi-Institutional Collaborative Cohort Study. Nutrients intake including calcium were estimated using a validated food-frequency questionnaire. Analysis using a general linear model revealed that dietary calcium intake was inversely associated with serum high-sensitivity C-reactive protein levels (p for trend <0.001) after adjustment for age, sex, research group, leisure-time physical activity, smoking habit, drinking habit, dietary intakes (energy, dietary fiber, saturated fatty acids and vitamin D) and menopausal status. The association was slightly attenuated after additional adjustment for body mass index; however, remained significant (p for trend = 0.008). There were no significant interactions between dietary calcium intakes and sex, body mass index, or vitamin D intake for high-sensitivity C-reactive protein levels. This study have demonstrated that dietary calcium intake was inversely associated with serum high-sensitivity C-reactive protein levels in the general population.

Association of genetic polymorphisms with erythrocyte traits: Verification of SNPs reported in a previous GWAS in a Japanese population

Erythrocyte count and volume are the commonly used hematological indices for anemia that change in various diseases. To date, however, only one study ever exists that addressed erythrocyte trait-associated single nucleotide polymorphisms (SNPs) in a Japanese population. Because that study was performed in patients with various diseases, we confirmed the reported associations in a general population. Participants in the current study were from the Shizuoka component of the Japan Multi-Institutional Collaborative Cohort Study, which included 4971 men and women aged 35 to 69years who were recruited between 2006 and 2007. We analyzed the association of seven selected SNPs with the following erythrocyte traits: red blood cell count, hemoglobin (Hb) and hematocrit (Ht) levels, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. The erythrocyte traits were regressed on a number of minor alleles of selected SNPs. Then we compared our findings with those from a genome-wide association study performed in a Japanese population. We replicated the association of ABO rs495828, PDGFRA-KIT rs218237, USP49-MED20-BSYL-CCND3 rs3218097, C6orf182-CD164 rs11966072, TERT rs2736100, and TMPRSS6 rs5756504 with erythrocyte traits in our independent Japanese population. In addition, we found a significant interaction between TERT rs2736100 and smoking habit that affected Hb and Ht levels.

Macronutrient intakes and serum oestrogen, and interaction with polymorphisms in CYP19A1 and HSD17B1 genes: a cross-sectional study in postmenopausal Japanese women.

Although higher circulating levels of oestrogen are related to postmenopausal breast cancer risk, limited information is available regarding effects of diet on endogenous oestrogen. Thus, we examined associations between macronutrient intakes and serum oestrogen with consideration of polymorphisms in oestrogen-metabolising genes. In this cross-sectional study, 784 naturally menopaused Japanese women aged 47-69 years were selected from participants of the Japan Multi-Institutional Collaborative Cohort Study. We documented dietary intakes, measured serum concentrations of oestrone (E1) and oestradiol (E2) and genotyped polymorphisms in oestrogen-metabolising CYP19A1 (rs4441215 and rs936306) and HSD17B1 (rs605059) genes. Trends and interactions were examined using linear regression models. In addition, we calculated the ratios of the oestrogen concentrations of the second to the highest quartiles (Q2-Q4) of dietary intake to those of the lowest quartiles (Q1). After adjustment for potential confounders, E2 was significantly associated with intake of carbohydrate and noodles; ratios of Q4 v. Q1 were 1·15 (95 % CI 1·04, 1·28) and 1·15 (95 % CI 1·04, 1·26), respectively. In contrast, E2 levels were inversely associated with intake of total energy, SFA and n-3 highly unsaturated fatty acids (n-3 HUFA); ratios of Q4 v. Q1 were 0·90 (95 % CI 0·82, 0·99), 0·89 (95 % CI 0·81, 0·98) and 0·91 (95 % CI 0·83, 1·00), respectively. In stratified analysis by polymorphisms, the rs605059 genotype of HSD17B1 significantly modified associations of E2 with intake of n-3 HUFA and fish; the associations were limited to those with the CC genotype. Macronutrient intakes were associated with serum E2 level, and these associations may be modified by HSD17B1 polymorphism in postmenopausal women.

Association between dietary patterns and serum adiponectin: a cross-sectional study in a Japanese population

The aim of this study was to evaluate the associations between dietary pattern, adiponectin and insulin resistance. The study population consisted of 612 men and women aged 35–69 years old who had participated in the baseline survey of Japan Multi-Institutional Collaborative Cohort (J-MICC) Study in Tokushima Prefecture. Diets and lifestyle related variables were assessed by questionnaires. Multiple regression analyses were used to analyse the relations between dietary patterns and high molecular weight (HMW) adiponectin. For further analysis, path analysis was used to test the hypothesised model of association between dietary pattern, serum adiponectin and insulin resistance. The result showed that higher score of bread and dairy pattern was directly associated with increased serum level of adiponectin in women, which was inversely related to homeostasis model assessment of insulin resistance (HOMA-IR). In conclusion, higher consumption of bread and dairy products, and low intake of rice may be associated with increased serum adiponectin in women.

Genetic Variants of RAMP2 and CLR are Associated with Stroke.

Aim: Stroke is associated closely with vascular homeostasis, and several complex processes and interacting pathways, which involve various genetic and environmental factors, contribute to the risk of stroke. Although adrenomedullin (ADM) has a number of physiological and vasoprotective functions, there are few studies of the ADM receptor system in humans. The ADM receptor comprises a calcitonin-receptor-like receptor (CLR) and receptor activity-modifying proteins (RAMPs). We analyzed single nucleotide polymorphisms (SNPs) in the RAMP2 and CLR genes to determine their association with stroke in the light of gene-environment interactions.Methods: Using cross-sectional data from the Japan Multi-Institutional Collaborative Cohort Study in the baseline surveys, 14,087 participants from 12 research areas were genotyped. We conducted a hypothesis-based association between stroke prevalence and SNPs in the RAMP2 and CLR genes based on data abstracted from two SNPs in RAMP2 and 369 SNPs in CLR. We selected five SNPs from among the CLR variants (rs77035639, rs3815524, rs75380157, rs574603859, and rs147565266) and one RAMP2 SNP (rs753152), which were associated with stroke, for analysis.Results: Five of the SNPs (rs77035639, rs3815524, rs75380157, rs147565266, and rs753152) showed no significant association with obesity, ischemic heart disease, hypertension, dyslipidemia, and diabetes. In the logistic regression analysis, rs574603859 had a lower odds ratio (0.238; 95% confidence interval, 0.076–0.745, adjusted for age, sex, and research area) and the other SNPs had higher odds ratios for association with stroke.Conclusions: This was the first study to investigate the relationships between ADM receptor genes (RAMP2 and CLR) and stroke in the light of gene-environment interactions in human.

Associations between Dietary Patterns, ADRβ2 Gln27Glu and ADRβ3 Trp64Arg with Regard to Serum Triglyceride Levels: J-MICC Study.

Interactions between dietary patterns and 2 β-adrenergic receptor (ADRβ) gene polymorphisms (ADRβ2 Gln27Glu and ADRβ3 Trp64Arg) were examined with regard to the effects on serum triglyceride levels. The cross-sectional study comprised 1720 men and women (aged 35–69 years) enrolled in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. Genotyping was conducted using a multiplex polymerase chain reaction-based invader assay. We used 46 items from a validated short food frequency questionnaire and examined major dietary patterns by factor analysis. We identified four dietary patterns: healthy, Western, seafood and bread patterns. There was no significant association between any dietary pattern and serum triglyceride levels. After a separate genotype-based analysis, significant interactions between ADRβ3 Trp64Arg genotype and the bread pattern (p for interaction = 0.01) were associated with serum triglyceride levels; specifically, after adjusting for confounding factors, Arg allele carriers with the bread pattern had lower serum triglycerides (p for trend = 0.01). However, the Trp/Trp homozygous subjects with the bread pattern showed no association with serum triglycerides (p for trend = 0.55). Interactions between other dietary patterns and ADRβ polymorphisms were not significant for serum triglyceride levels. Our findings suggest that ADRβ3 polymorphism modifies the effects of the bread pattern on triglyceride levels.

Effects of self-reported calorie restriction on correlations between SIRT1 polymorphisms and body mass index and long-term weight change

SIRT1 acts as a cellular sensor to detect energy availability and modulates fat and glucose metabolism. This study assessed the effects of self-reported calorie restriction (CR) and exercise on correlations between SIRT1 polymorphisms and body mass index (BMI) and long-term weight change. This cross-sectional study enrolled 4023 subjects aged 35–69years (1847 men and 2176 women) selected from participants in the Japan Multi-Institutional Collaborative Cohort Study. This study was based on a self-administered questionnaire. No significant correlations between SIRT1 polymorphisms and BMI or long-term weight change were found in either the CR or the active groups. In the no-CR group, women with the rs1467568 G allele had a higher BMI than women without (p=0.02). Moreover, women with the rs7895833 A or rs1467568 G allele gained more weight from the age of 20years than women without these alleles (p=0.03 for rs7895833 and p=0.003 for rs1467568). In addition, the odds ratios (95% confidence intervals) of these alleles for overweight (BMI >27.5kg/m2) were significantly high in the no-CR women group (1.78 (1.06–2.99) for rs7895833 and 1.88 (1.13–3.15) for rs1467568) but not in the CR group. The results of this study suggest that CR might override the genetic contributions of the SIRT1 rs7895833 A and rs1467568 G alleles to BMI and long-term weight change.

Validity of self-reported number of teeth and oral health variables

BackgroundOral condition and number of teeth were investigated by questionnaire in the Japan Multi-Institutional Collaborative Cohort (J-MICC Study). The aim of the present study was to assess the validity of the tooth number measure by comparing the self-reported number of teeth with the number of teeth determined at clinical dental examination.MethodsA self-administered questionnaire and dental examination were performed by 1275 participants of a company medical examination who requested dental check-up and 377 subjects of the J-MICC study. The validity of the tooth number measure was assessed by comparing the self-reported number of teeth with that determined at clinical examination. Spearman’s rank correlation coefficient was calculated to quantitatively evaluate the validity.ResultsIn males, the mean clinically-examined and self-reported numbers of teeth were 26.5 and 24.8 teeth, respectively. In females, the mean clinically-examined and self-reported numbers of teeth were 26.4 and 25.5 teeth, respectively. There was a tendency toward underestimation of the number of natural teeth by self-reporting. A significant correlation was observed between the clinically-examined and self-reported numbers of teeth in total (ρ = 0.69) and both males (ρ = 0.70) and females (ρ = 0.67).ConclusionsThe self-reported oral health variables were valid and reflected clinical status. Further revision of the question on the remaining tooth in the questionnaire improves the validity of self-reported number of teeth.

ALDH2 polymorphism is associated with fasting blood glucose through alcohol consumption in Japanese men.

Associations between alcohol consumption and type 2 diabetes risk are inconsistent in epidemiologic studies. This study investigated the associations of ADH1B and ALDH2 polymorphisms with fasting blood glucose levels, and the impact of the associations of alcohol consumption with fasting blood glucose levels in Japanese individuals. This cross-sectional study included 907 men and 912 women, aged 35-69 years. The subjects were selected from among the Japan Multi-institutional Collaborative Cohort study across six areas of Japan. The ADH1B and ALDH2 polymorphisms were genotyped by Invader Assays. The ALDH2 Glu504Lys genotypes were associated with different levels of fasting blood glucose in men (P = 0.04). Mean fasting glucose level was positively associated with alcohol consumption in men with the ALDH2 504 Lys allele (P trend = 0.02), but not in men with the ALDH2 504Glu/Glu genotype (P trend = 0.45), resulting in no statistically significant interaction (P = 0.38). Alcohol consumption was associated with elevated fasting blood glucose levels compared with non-consumers in men (P trend = 0.002). The ADH1B Arg48His polymorphism was not associated with FBG levels overall or after stratification for alcohol consumption. These findings suggest that the ALDH2 polymorphism is associated with different levels of fasting blood glucose through alcohol consumption in Japanese men. The interaction of ALDH2 polymorphisms in the association between alcohol consumption and fasting blood glucose warrants further investigation.

Metallothionein MT2A A-5G Polymorphism as a Risk Factor for Chronic Kidney Disease and Diabetes: Cross-Sectional and Cohort Studies.

Metallothioneins (MTs) are proteins that protect cells from toxic agents such as heavy metal ions or reactive oxygen species. MT2A A-5G is a single nucleotide polymorphism in the promoter region of the MT2A gene, and the minor G allele results in lower transcription efficiency. We aimed to elucidate associations between MT2A A-5G and risks of 2 diseases potentially related to lowered MT expression, chronic kidney disease (CKD), and diabetes mellitus (DM), in a community-dwelling population. Study subjects were Nagoya city residents participating in the Japan Multi-Institutional Collaborative Cohort Study (J-MICC) Daiko Study, comprised 749 men and 2,025 women, aged 39–75 years. CKD (>stage 3) and DM were defined by standard guidelines. Associations were evaluated using logistic regression models with adjustments for age, sex and potential confounders in a cross-sectional study, and verified in a 5-year longitudinal study. Odds ratios (OR [95% confidence interval]) were calculated relative to the AA genotype. Serum MT (I + II), Cd and zinc levels were also determined by genotype. The OR of the GG genotype for CKD risk was 3.98 (1.50, 10.58) in the cross-sectional study and 5.17 (1.39, 19.28) in the longitudinal study. The OR of the GA genotype for DM was 1.86 (1.26, 2.75) in the cross-sectional study and 2.03 (1.19, 3.46) in the longitudinal study. MT2A A-5G may be associated with CKD and DM risks. This polymorphism is a promising target for evaluations of CKD and DM risks with possible involvement of low-dose chronic exposure to environmental pollutants.

Matrix metalloproteinase9 gene polymorphisms are associated with a multiple family history of gastric cancer.

A family history of gastric cancer (GC) is a well-known risk factor of GC. Genetic variations in genes of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have been related to the risk of GC, but their association with familial background is not clear. We investigated whether individuals with a multiple family history of GC have more risk genotypes of MMP/TIMP genes. We genotyped ten common functional polymorphisms of MMP/TIMP genes in 4427 individuals aged 35-69years without a history of GC who were enrolled in the Japan Multi-institutional Collaborative Cohort Study. Individuals who have two or more first-degree relatives (parents and siblings) with GC were categorized as having a multiple family history. Odds ratios (ORs) for multiple family history compared with no family history were calculated. MMP9 279QQ (rs17576) was more frequently observed in individuals whose both parents had a history of GC (n=23) and in individuals for whom one parent and their sibling(s) had a history of GC (n=36) compared with those with no family history (n=3816) [30.4% vs 11.6%, OR 4.34, 95% confidence interval (CI) 1.45-13.03 and 16.7% vs 11.6%, OR 2.26, 95% CI 0.81-6.27 after adjustment for age, sex, and current smoking]. The population attributable fraction was 38.1%. The haplotype MMP9-1562C/279Q/668Q was more frequently observed in individuals whose both parents had a history of GC and in individuals for whom one parent and their sibling(s) had a history of GC compared with those with no family history (OR 3.35, 95% CI 0.75-14.96 and OR 3.51, 95% CI 1.35-9.15 respectively). MMP9 polymorphisms were associated with a multiple family history of GC. Screening for these genotypes together with familial background may help us to identify individuals at an increased risk of GC.

Influence of cigarette smoking and inflammatory gene polymorphisms on glycated hemoglobin in the Japanese general population.

ObjectiveInflammation is closely involved in the development of type 2 diabetes, and cigarette smoking acts as potent inducer of inflammation. We therefore investigated interactions between inflammation-related gene polymorphisms and cigarette smoking on glycated hemoglobin (HbA1c) in the Japanese general population.MethodWe conducted a cross-sectional study using data collected from 2619 Japanese (1274 males and 1345 females) 40–69 years of age who participated in baseline survey of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study (2005–2008). Eight polymorphisms in seven genes (interleukin [IL]-1β, IL-2, IL-4, IL-8, IL-10, IL-13 and tumor necrosis factor-α) were determined using the Invader assay. The interactions of smoking and gene polymorphisms on HbA1c levels were analyzed using multiple linear and logistic regression models and analysis of covariance with adjustment for potential confounders.ResultsAmong the eight polymorphisms, only one significant interaction was detected for IL-1β T-31C (P < 0.0001). Among the subjects carrying TT genotype, current heavy smokers (≥ 20 cigarettes/day) had higher HbA1c (5.83 [95% confidence interval 5.67–5.99] %) versus all other smoking status groups (never 5.49 [5.41–5.56] %, former 5.54 [5.43–5.65] %, current moderate [< 20 cigarettes/day] 5.50 [5.30–5.69] %), whereas such differences were not observed in the subjects with C allele. The logistic regression analyses regarding high-normal HbA1c levels showed a similar pattern of results.ConclusionSmoking status did not interact with any other inflammation-related polymorphisms except for IL-1β T-31C. Heavy smokers harboring the TT genotype of IL-1β T-31C polymorphism show a greater adverse effect of smoking on HbA1c levels among Japanese middle-aged subjects.

Variant of the clock circadian regulator (CLOCK) gene and related haplotypes are associated with the prevalence of type 2 diabetes in the Japanese population.

Circadian rhythm disruptions can cause various health disorders. The present study evaluated associations between single nucleotide polymorphisms in the core circadian gene clock circadian regulator (CLOCK) and the prevalence of type 2 diabetes (T2D) in the Japanese population. Cross-sectional data were analyzed from 2485 subjects (1243 men, 1242 women; age 35-69 years) enrolled in the baseline surveys of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. Associations between three CLOCK gene polymorphisms (rs1801260, rs3736544, and rs4864548) and the prevalence of obesity (body mass index [BMI] ≥25 kg/m(2) ), overweight (BMI ≥23 kg/m(2) ), and T2D were evaluated by logistic regression analyses; haplotype analysis and stratified analyses for the prevalence of diabetes were also conducted. Compared with those who were homozygous for the respective major alleles, subjects with the rs1801260 minor allele C had a significantly higher odds ratio (1.5; 95% confidence interval 1.1-2.1) for the prevalence of diabetes after adjustment for potential confounding factors, including BMI. When stratified by overweight, the associations between rs1801260 and the prevalence of diabetes were marked and significant in non-overweight subjects, but not in overweight subjects. The TGA (rs1801260-rs3736544-rs4864548) haplotype was associated with a lower prevalence of diabetes, whereas the CGG haplotype was associated with a higher prevalence of diabetes. Variant of the CLOCK gene and related haplotypes are associated with the prevalence of T2D in the Japanese population, in which obesity is less common, and the association between CLOCK gene variant at rs1801260 and the prevalence of diabetes is enhanced in normal-weight subjects.

Genetic variants of SLC17A1 are associated with cholesterol homeostasis and hyperhomocysteinaemia in Japanese men.

Hyperuricaemia is an undisputed and highly predictive biomarker for cardiovascular risk. SLC17A1, expressed in the liver and kidneys, harbours potent candidate single nucleotide polymorphisms that decrease uric acid levels. Therefore, we examined SLC17A1 polymorphisms (rs1165196, rs1179086, and rs3757131), which might suppress cardiovascular risk factors and that are involved in liver functioning, via a large-scale pooled analysis of the Japanese general population in a cross-sectional study. Using data from the Japan Multi-Institutional Collaborative Cohort Study, we identified 1842 participants of both sexes, 35–69-years-old, having the requisite data, and analysed their SLC17A1 genotypes. In men, logistic regression analyses revealed that minor alleles in SLC17A1 polymorphisms (rs1165196 and rs3757131) were associated with a low-/high-density lipoprotein cholesterol ratio >2.0 (rs1165196: odds ratio [OR], 0.703; 95% confidence interval [CI], 0.536–0.922; rs3757131: OR, 0.658; 95% CI, 0.500–0.866), and with homocysteine levels of >10.0 nmol/mL (rs1165196: OR, 0.544; 95% CI, 0.374–0.792; rs3757131: OR, 0.509; 95% CI, 0.347–0.746). Therefore, these polymorphisms had dominant negative effects on cholesterol homeostasis and hyperhomocysteinaemia, in men, independent of alcohol consumption, physical activity, or daily energy and nutrition intake. Thus, genetic variants of SLC17A1 are potential biomarkers for altered cholesterol homeostasis and hyperhomocysteinaemia in Japanese men.

Association between brain-muscle-ARNT-like protein-2 (BMAL2) gene polymorphism and type 2 diabetes mellitus in obese Japanese individuals: A cross-sectional analysis of the Japan Multi-institutional Collaborative Cohort Study

AimsBrain-muscle-Arnt-like protein-1 (BMAL1) and BMAL2 genes are essential components of the circadian clock, and are considered to be involved in glucose homeostasis. We examined whether single nucleotide polymorphisms (SNPs) of BMAL1 and BMAL2 were associated with the prevalence of type 2 diabetes (T2DM) in the general Japanese population. MethodsWe studied 2467 subjects (1232 men and 1235 women, 35–69 years old), including 105 men and 57 women with T2DM, from the participants of the Japan Multi-institutional Collaborative Cohort Study. The association between SNPs in the BMAL1 (rs11022775 and rs2290035) and BMAL2 (rs7958822) genes and T2DM were analyzed by multiple logistic regression after adjustment for potential confounders. Analysis was also performed after stratification by body mass index (≥25kg/m2 and <25kg/m2) to investigate an interaction between genotypes and obesity. ResultsThe A/G and A/A genotypes of BMAL2 rs7958822 showed significantly higher adjusted odds ratios (OR) for T2DM than the G/G genotype among obese men (OR=2.2, 95% confidence intervals [CI] 1.1, 4.6, P for interaction=0.0495) and obese women (OR=2.7, 95% CI 1.1, 6.7, P for interaction=0.199). There were no significant associations between BMAL1 rs11022775 or rs2290035 genotypes and T2DM. ConclusionsTo the best of our knowledge, this is the first study to show the significant association between BMAL2 rs7958822 genotype and T2DM among obese subjects.

No association between Helicobacter pylori infection and diabetes mellitus among a general Japanese population: a cross-sectional study.

Several case-control studies have reported that patients with diabetes mellitus (DM) had a higher prevalence of Helicobacter pylori infection than those without DM, but these findings remain equivocal. Additionally, there are few studies examining associations between East Asian CagA-positive H. pylori and DM. This cross-sectional study aimed to investigate whether H. pylori infection was a possible risk factor for DM in a general Japanese population. The study included 5165 subjects (1467 men, 3698 women) aged 35–69 years from the Daiko Study, part of the Japan Multi-Institutional Collaborative Cohort Study. A urinary anti-H. pylori antibody was used to detect H. pylori infection. The medical history of physician-diagnosed DM was confirmed by self-administered questionnaire. The odds ratios (ORs) and their 95 % confidence intervals (CIs) for DM (current and former) were calculated using unconditional logistic regression analysis, adjusting for age, sex, educational status, alcohol use, smoking status, body mass index, energy intake, and physical activity. The prevalence of DM was 4.6 % (95 % CI 3.7–5.6 %) among 1878 participants with H. pylori infection and 3.2 % (2.6–3.8 %) among 3287 without the infection (p = 0.009). The crude, age-adjusted, and multivariate-adjusted ORs for DM in those with the infection relative to those without were 1.47 (95 % CI 1.10–1.97), 1.02 (0.76–1.38), and 0.97 (0.71–1.32), respectively. We found a significantly higher DM prevalence among those with H. pylori infection than among those without. However, almost all the difference in prevalence could be explained by the older age of those infected. Our findings did not support an association between H. pylori infection and DM.

Polymorphisms in CYP19A1, HSD17B1 and HSD17B2 genes and serum sex hormone level among postmenopausal Japanese women

ObjectiveExtraovarian sex hormone production plays an important role in estrogen biosynthesis in postmenopausal women. We examined possible associations between serum sex hormone level and polymorphisms in CYP19A1, HSD17B1, and HSD17B2. We also assessed possible interaction between these polymorphisms and current overweight. MethodsWe conducted a cross-sectional study. 785 Japanese natural postmenopausal women were randomly selected from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study database. Information on lifestyle factors was obtained from a self-administered questionnaire. Serum estrogens and androgens levels were measured by liquid chromatography–tandem mass spectrometry. Four tag SNPs (single nucleotide polymorphisms) of CYP19A1, one missense SNP of HSD17B1 and three tag SNPs of HSD17B2 were examined by Invader assay. A trend test was conducted using linear regression. ResultsAfter adjustment for multiple comparisons, we found that rs4441215 and rs936306 in CYP19A1 and rs4888202 and rs2955160 in HSD17B2 were associated with differences in serum estrone level. Further, rs4441215 and rs936306 were associated with differences in serum estradiol level. None of these polymorphisms showed a significant interaction with current body mass index (BMI). ConclusionsOur findings suggested that CYP19A1 and HSD17B2 polymorphisms might be associated with circulating sex hormone levels in Japanese postmenopausal women, independent of current BMI.

Factors associated with non-participation in a face-to-face second survey conducted 5 years after the baseline survey.

BackgroundNon-participation in second surveys is reported to be associated with certain baseline characteristics; however, such data are unavailable for Japanese populations. Although disease incidence during follow-up might influence participation, few reports have addressed this possibility. This study sought to identify factors associated with non-participation in a second survey of a population-based cohort, and to evaluate the influence of self-reported disease incidence on non-participation.MethodsAfter excluding participants who left the area (n = 423), died (n = 163), and withdrew from the study (n = 9) among 12 078 participants in a baseline survey for the Japan Multi-Institutional Collaborative Cohort Study in the Saga region between 2005 and 2007, 11 483 people were invited by mail to participate in a face-to-face second survey between 2010 and 2012. The 5-year clinical health history of non-participants was assessed by mail or telephone. Baseline characteristics and self-reported clinical outcomes of non-participants were compared with those of participants.ResultsAmong 11 483 people, 8454 (73.6%) participated in the second survey, and 2608 out of 3029 non-participants answered mail or telephone health surveys. Female sex, youngest and oldest ages, lower education, lower occupational class, current smoking, lower physical activity level, shorter sleep time, obesity, and constipation were associated with non-participation. Light drinking (0.1–22.9 g ethanol/day) was associated with participation. Non-participants reported a significantly higher incidence of cancer and a significantly lower proportion of hypertension compared with participants.ConclusionsBoth baseline characteristics and disease incidence during the follow-up period had significant associations with non-participation in the face-to-face second survey.