Intraindividual variation in histone acetylation and its impact on autoimmune thyroid diseases.

Autoimmune thyroid diseases (AITDs), such as Graves' disease (GD) and Hashimoto's disease (HD), are organ-specific autoimmune diseases. Histone acetylation, especially that of histone H3, is an epigenetic mechanism that regulates gene expression and is associated with the development of autoimmune diseases. However, physiological variations in histone acetylation are not yet clear, and we believe that physiological variations should be examined prior to analysis of the role of histone H3 in the pathogenesis of AITDs. In this study, we analyzed histone H3 acetylation levels in peripheral blood mononuclear cells (PBMCs) using a histone H3 total acetylation detection fast kit. Blood samples were collected before meals, between 8:30-9:00 am, daily for 10 weeks to evaluate the daily variation. At 4 days, blood was also collected before meals three times a day (at 8:30-9:00, 12:30-13:00, and 16:30-17:00) to evaluate circadian variation. Then, histone H3 acetylation levels were evaluated in AITD patients to clarify the association with the pathogenesis of AITD. Although we could not find a common pattern of circadian variance, we observed daily variation in histone H3 acetylation levels, and their coefficient of variances (CVs) were approximately 48.3%. Then, we found that histone H3 acetylation levels were significantly lower in GD and HD patients than in control subjects and these differences were larger than the daily variation in histone acetylation. In conclusion, histone H3 acetylation levels were associated with the development of AITD, even allowing for daily variation.

Genome-wide association study of clinically defined gout identifies multiple risk loci and its association with clinical subtypes.

OBJECTIVE: Gout, caused by hyperuricaemia, is a multifactorial disease. Although genome-wide association studies (GWASs) of gout have been reported, they included self-reported gout cases in which clinical information was insufficient. Therefore, the relationship between genetic variation and clinical subtypes of gout remains unclear. Here, we first performed a GWAS of clinically defined gout cases only. METHODS: A GWAS was conducted with 945 patients with clinically defined gout and 1213 controls in a Japanese male population, followed by replication study of 1048 clinically defined cases and 1334 controls. RESULTS: Five gout susceptibility loci were identified at the genome-wide significance level (p<5.0×10(-8)), which contained well-known urate transporter genes (ABCG2 and SLC2A9) and additional genes: rs1260326 (p=1.9×10(-12); OR=1.36) of GCKR (a gene for glucose and lipid metabolism), rs2188380 (p=1.6×10(-23); OR=1.75) of MYL2-CUX2 (genes associated with cholesterol and diabetes mellitus) and rs4073582 (p=6.4×10(-9); OR=1.66) of CNIH-2 (a gene for regulation of glutamate signalling). The latter two are identified as novel gout loci. Furthermore, among the identified single-nucleotide polymorphisms (SNPs), we demonstrated that the SNPs of ABCG2 and SLC2A9 were differentially associated with types of gout and clinical parameters underlying specific subtypes (renal underexcretion type and renal overload type). The effect of the risk allele of each SNP on clinical parameters showed significant linear relationships with the ratio of the case-control ORs for two distinct types of gout (r=0.96 [p=4.8×10(-4)] for urate clearance and r=0.96 [p=5.0×10(-4)] for urinary urate excretion). CONCLUSIONS: Our findings provide clues to better understand the pathogenesis of gout and will be useful for development of companion diagnostics.

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.

ATP-binding cassette transporter A1 (ABCA1) R219K (G1051A, rs2230806) polymorphism and serum high-density lipoprotein cholesterol levels in a large Japanese population: cross-sectional data from the Daiko Study.

Among polymorphisms in ATP-binding cassette transporter A1 (ABCA1) gene, the available evidence demonstrates that the ABCA1 R219K polymorphism (G1051A, rs2230806) K allele is associated with a higher high-density lipoprotein cholesterol (HDL- C) level and may play a protective role against coronary artery disease (CAD) risk in Asians and Caucasians. The findings from many underpowered studies from Asian countries (n=71-597), however, still remain inconsistent. The objective of this study was to overcome the limitations of previous studies in Asia and provide solid epidemiologic evidence. Subjects were participants of a cohort study, who visited the Daiko Medical Center in Nagoya, Japan. The cohort study belongs to the Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study). In the Daiko Study, 5,133 participants (1,458 men and 3,675 women) aged 35-69 years enrolled from 2008 through 2010 were eligible for the analyses. The ABCA1 polymorphism was genotyped by the polymerase chain reaction with confronting two-pair primers (PCR-CTPP) method. Among all the subjects, the genotype frequencies were 23.9% (n=1,225) for RR, 49.3% (n=2,532) for RK, and 26.8% (n=1,376) for KK, which was in Hardy-Weinberg's equilibrium (P =0.36). Background characteristics did not significantly differ among the genotypes including alcohol and tobacco use. The mean ± SD of HDL-C concentration was higher in men and women with RK or KK genotype than those with RR, although the difference between these genotypes was not statistically significant in both sexes (P =0.31 in men and 0.26 in women by ANOVA). In the multiple linear regression analysis to estimate the independent effects of the R219K polymorphism on HDL-C level, however, the number of K allele was significantly correlated with an increased level of HDL-C (trend P=0.033). Those with the KK genotype showed a significantly higher HDL-C concentration compared with those with the RR genotype by a mean of 1.18 mg/dL. The R219K polymorphism of ABCA1 independently associated with serum level of HDL-C in a large Japanese population.

Common variants of a urate-associated gene LRP2 are not associated with gout susceptibility.

A recent genome-wide association study revealed that there is an association between serum uric acid (SUA) levels and rs2544390, a common variant in low-density lipoprotein-related protein 2 (LRP2/Megalin) gene. Two other variants of LRP2, rs2229268 and rs3755166, are also found to have associations with dyslipidemia and Alzheimer's disease, respectively, which also could have a relationship with SUA in human. Although no studies report that LRP2 transports urate, LRP2 is a multi-ligand receptor and expresses in many tissues including kidney, suggesting a direct and/or indirect relationship with gout. In the present study, we investigated the association between gout and these variants of LRP2 with 741 clinically diagnosed male gout patients and 1,302 controls. As a result, the three common LRP2 variants, rs2544390, rs2229268 and rs3755166, showed no association with gout (P = 0.76, 0.55, and 0.22, respectively). Our study is the first to reveal that an SUA-related gene LRP2 is not involved in gout susceptibility.

ASSOCIATIONS BETWEEN BODY MASS INDEX AND SERUM URIC ACID LEVELS IN A JAPANESE POPULATION WERE SIGNIFICANTLY MODIFIED BY LRP2 rs2544390.

The genome-wide association study identified associations between the LRP2 polymorphism rs2544390 and serum uric acid (SUA) levels in a Japanese population. Our previous study on the LRP2 rs2544390 polymorphism identified an interaction between SUA and alcohol consumption. Here, we investigated an interaction with body mass index (BMI) using the same dataset. Subjects were 3,742 health checkup examinees (2,544 males and 1,198 females) aged 35-69 years. Those with the SLC22A12 258WW genotype, SLC2A9 rs11722228 C allele, and ABCG2 126QQ genotype and 141Q allele were selected for analysis to remove the strong influences of these genetic traits. In males, the odds ratio of BMI ≥25.0 relative to BMI <18.5 for hyperuricemia (SUA ≥7 mg/dL and/or under medication for hyperuricemia) was 6.58 (95% confidence interval [CI], 0.84-51.32) for CC, 10.08 (2.38-42.83) for CT, and 2.53 (0.54-11.78) for TT. The interaction was 0.59 (p=0.029) from the model including BMI (<25.0 and ≥25.0), genotype (CC/CT and TT), and the multiplicative interaction term between BMI ≥25.0 and the TT genotype. In females, the odds ratio of BMI ≥25.0 relative to BMI <18.5 for high SUA (≥5 mg/dL and/or under medication for hyperuricemia) was 6.35 (95%CI, 1.68-24.08) for CC, 4.55 (1.85-11.18) for CT, and 5.93 (1.97-17.90) for TT. The interaction term was significant in the opposite direction for females (OR=2.75, p=0.011). The association between BMI and SUA was therefore modified by the LRP2 polymorphism in this Japanese population.

The Inverse Association between the Frequency of Forest Walking (Shinrin-yoku) and the Prevalence of Insomnia Symptoms in the General Japanese Population: A Japan Multi-Institutional Collaborative Cohort Daiko Study.

Since a single forest walk (Shinrin-yoku or forest bathing) session is reported to improve sleep temporarily, occasional forest walks may have a positive effect on daily sleep. Therefore, this study aimed to examine whether more frequent forest walking is associated with better daily sleep conditions. Data from the second survey of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Daiko Study conducted among residents of Nagoya City, Japan, were used. The study design was a cross-sectional study. In total, 2044 participants (529 men and 1515 women; age, mean ± standard deviation: 58.8 ± 9.9 years) were included in the analysis. Frequent forest walks were associated with a low percentage of insomnia symptoms (Insomnia Severity Index ≥10) in women, but not in men. The adjusted odds ratio for the group that rarely took forest walks with reference to the group that engaged in the activity once a month or more often was 2.04 (95% confidence interval: 1.29-3.23) in women. Forest walk frequency was not significantly associated with sleep duration or sleep efficiency as measured by actigraphy in either men or women. In conclusion, the results suggested that increasing the frequency of forest walks or Shinrin-yoku may be effective in preventing insomnia in women.

Association between dysphagia risk and sleep quality in community-dwelling older adults: A cross-sectional study.

Objectives: Exploring the effects of swallowing function on sleep quality could provide valuable insights into the potential impact of reduced swallowing function on sleep. However, pertinent studies are limited. Therefore, this study aimed to investigate the relationship between dysphagia risk and sleep health in community-dwelling older adults. Methods: Data for this cross-sectional study were obtained from the Shizuoka and Daiko studies conducted as part of the Japan Multi-Institutional Collaborative Cohort Study. Information on demographics, overall lifestyle, dysphagia risk, as well as sleep quality, duration, satisfaction, and regularity, was obtained using a self-administered questionnaire. Dysphagia risk and sleep quality were assessed using the Dysphagia Risk Assessment Questionnaire for the Community-dwelling Elderly and the Japanese version of the Pittsburgh Sleep Questionnaire Index, respectively. Multivariate logistic regression, adjusted for covariates, was employed to assess the association between dysphagia risk and sleep health. Results: Among the 3058 participants (1633 males, 1425 females) aged ≥60 years, 28.0 % exhibited dysphagia risk, and 19.1 % reported poor sleep quality. Those with dysphagia risk were more likely to experience poor sleep quality than those without dysphagia risk. In male participants, dysphagia was significantly associated with poor sleep quality, unsatisfactory sleep, and sleep irregularity, but was not significantly associated with unsatisfactory or irregular sleep in female participants. The Japanese version of the Pittsburgh Sleep Questionnaire Index components-subjective sleep quality, sleep latency, sleep disturbances, and daytime dysfunction-were associated with dysphagia risk in both sexes. Conclusions: Dysphagia risk is associated with sleep quality in older individuals in Japan. Thus, preserving swallowing function may contribute to enhancing sleep quality.

Significant interaction between RETN -420 G/G genotype and lower BMI on decreased risk of type 2 diabetes mellitus (T2DM) in Japanese--the J-MICC Study.

We examined the association of the RETN (resistin) -420 C>G polymorphism (rs1862513) with risk of diabetes mellitus (DM), considering lifestyle factors, in Japanese. Subjects were participants of J-MICC Study, where 2,651 participants aged 35-69 years provided their blood for genotyping and lifestyle data after informed consent. Odds ratio (OR) of DM for RETN-420 G/G genotype was estimated using unconditional logistic regression model. Statistically significant interaction on risk of DM was observed between RETN-420 G/G genotype and BMI<25 (OR for interaction = 0.12; P = 0.046), and when subjects with RETN-420 C/C+C/G and BMI ≥ 25 (n = 69 for DM and 544 for non-DM) were defined as the reference, the adjusted ORs for subjects with RETN-420 G/G genotype and BMI>25 (n = 10 for DM and 111 for non-DM), RETN-420 C/C+C/G and BMI<25 (n = 81 for DM and 1,605 for non-DM), and RETN-420 G/G and BMI<25 (n = 1 for DM and 230 for non-DM) were demonstrated to be 0.72 (95% confidence interval: 0.36-1.46), 0.40 (0.28-0.56) and 0.03 (0.005-0.25), respectively. The present study revealed the significant interaction of RETN-420 G/G genotype with lower BMI on the decreased risk of DM, but the direction was opposite to the reported ones in Japanese. We should be careful in interpretation of the present study results because of the limited sample sizes. Further investigation of this association as well as of the actual biological roles of RETN in the genesis of human metabolic disorders including DM will be required.

No association between MTHFR C677T and serum uric acid levels among Japanese with ABCG2 126QQ and SLC22A12 258WW.

Several genome-wide association studies (GWAS) have revealed that single nucleotide polymorphisms (SNPs) of ABCG2 and SLC22A12 were strongly associated with serum uric acid (SUA), but those of methylene tetrahydrofolate reductase (MTHFR) were not. However, there were several studies indicating the association with MTHFR C677T polymorphism. This study examined the association with the polymorphism, taking into account the genotypes of ABCG2 Q126X and SLC22A12 W258X. Subjects were 5,028 health checkup examinees of Seirei Preventive Health Care Center (3,416 males and 1,612 females) aged 35 to 69 years, who participated in the Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study). Hyperuricemia was defined as SUA equal to 7 mg/dL or over. The genotype frequency was 35.9% for CC, 48.1% for CT, and 16.0% for TT, being in Hardy-Weinberg equilibrium (p=0.90). Among 4,425 participants with ABCG2 126QQ and SLC22A12 258WW who were not under medication for hyperuricemia, the mean SUA was 5.6 mg/dL, 5.6 mg/dL, and 5.7 mg/dL, respectively. When 114 participants with ABCG2 126QQ and SLC22A12 258WW under medication for hyperuricemia were included in hyperuricemia cases, the sex-age adjusted odds ratio (OR) of hyperuricemia was not significant; OR=1.00 (95% confidence interval, 0.89-1.24) for CT genotype and OR=0.98 (0.84-1.32) for TT genotype, relative to CC genotype. The present study indicated no association between SUA and MTHFR C677T genotype, after the influences of ABCG2 Q126X and SLC22A12 W258X were removed.

DPP4 genetic variants influence baseline prostate-specific antigen levels: the J-MICC study.

Prostate specific antigen (PSA) testing plays a major role in prostate cancer screening; however, the low positive predictive value of PSA testing leads to many unnecessary biopsies. Genetic background is one of factors that could cause it. That's why an association between genetic background and PSA levels should be elucidated. This study aimed to investigate whether DPP4 genetic variants are associated with baseline PSA levels. A cross-sectional study was performed on 2,074 Japanese men aged between 35 and 69 in the Shizuoka area from the Japan Multi-institutional Collaborative Cohort (J-MICC) Study. Three DPP4 tagging single nucleotide polymorphisms (SNPs) were selected for genotyping: rs3788979 (A/G), rs7608798 (T/C), and rs2268889 (A/G). Higher mean serum PSA levels were significantly associated with an increase in the number of the rs7608798 C allele (p for trend = 0.02). A stratified analysis by age groups demonstrated that PSA levels had positive significant trends with the numbers of the minor alleles of rs3788979 or rs7608798 in the oldest group (men aged between 60 and 69) (p for trend=0.004 for rs3788979 and p for trend=0.001 for rs7608798). Haplotype analysis showed that the C-A (rs7608798-rs2268889) haplotype was significantly associated with increased PSA levels (p=0.006), compared with the most common haplotype, T-A. In summary, our study suggests that DPP4 genetic variants influence baseline PSA levels, especially in men aged between 60 and 69.

Polymorphisms in genes encoding antioxidant enzymes (SOD2, CAT, GPx, TXNRD, SEPP1, SEP15 and SELS) and risk of chronic kidney disease in Japanese - cross-sectional data from the J-MICC study.

Chronic kidney disease (CKD) is well known as a strong risk factor for both of end-stage renal disease and cardiovascular disease. To clarify the association of polymorphisms in the genes encoding antioxidant enzymes (SOD2, CAT, GPx, TXNRD, SEPP1, SEP15 and SELS) with the risk of CKD in Japanese, we examined this association using the cross-sectional data of Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. The subjects were 3,285 men and women, aged 35-69 years, selected from J-MICC Study participants for whom genotyping were conducted by multiplex polymerase chain reaction-based Invader assay. The prevalence of CKD was determined for CKD stages 3-5 (eGFR <60 ml/min/1.73 m(2)). When those with CAT C-262T C/C were defined as reference, those with CAT C-262T C/T demonstrated the OR for CKD of 0.67 (95% CI 0.43-1.06) with the marginally significant trend for decreased odds ratio with increasing numbers of T allele (p = 0.070). There were no significant associations between the other polymorphisms with CKD risk. The present study found a marginally significant trend of the decreased risk of CKD with increasing numbers of T allele of CAT, which may suggest the possibility of personalized risk estimation of this life-limiting disease in the near future.

Effect of the PPARG2 Pro12Ala polymorphism and clinical risk factors for diabetes mellitus on HbA1c in the Japanese general population.

BACKGROUND: Although the peroxisome proliferator-activated receptor-γ2 (PPARG2) Pro12Ala gene variant is associated with diabetes mellitus, the associations and interactions of this polymorphism and known clinical risk factors with glycated hemoglobin (HbA1c) remain poorly understood. We investigated if carrying the Ala allele was inversely associated with HbA1c level and examined possible interactions. METHODS: This cross-sectional analysis used data collected from 1281 men and 1356 women aged 40 to 69 years who completed the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study. PPARG2 polymorphism was determined by multiplex polymerase chain reaction (PCR)-based Invader assay. Multiple linear regression and ANCOVA were used to control for confounding variables (age, body mass index [BMI], energy intake, alcohol, smoking, physical activity, and family history of diabetes) and examine possible interactions. RESULTS: After adjustment, the Ala allele was significantly inversely associated with HbA1c in women but not in men. Older age, BMI, and family history of diabetes were associated with higher HbA1c in both sexes. When stratified by PPARG2 genotype, these associations were observed in subjects with the Pro12Pro genotype but not in Ala allele carriers. A significant interaction of genotype and BMI on HbA1c was observed in women. Older age, BMI, and family history of diabetes were significantly associated with high-normal HbA1c (≥5.7% NGSP), whereas PPARG2 polymorphism was not. CONCLUSIONS: Although PPARG2 Pro12Ala polymorphism might attenuate associations between known risk factors and HbA1c level, it had a small effect on high-normal HbA1c, as compared with clinical risk factors, in the general population.

Associations of apolipoprotein A5 (APOA5), glucokinase (GCK) and glucokinase regulatory protein (GCKR) polymorphisms and lifestyle factors with the risk of dyslipidemia and dysglycemia in Japanese - a cross-sectional data from the J-MICC Study.

This study examined the associations of the APOA5 T-1131C (rs662799), G553T (Cys185Gly, rs2075291), GCK G-30A (rs1799884), GCKR A/G at intron 16 (rs780094) and T1403C (Leu446Pro, rs1260326) polymorphisms with serum lipid and glucose levels in Japanese, considering lifestyle factors. Study subjects were 2,191 participants (aged 35-69 years, 1,159 males) enrolled in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. Dyslipidemia was defined as fasting serum triglycerides (FTG) ≥ 150 mg/dL and/or HDL-cholesterol (HDL-C) < 40 mg/dL, while dysglycemia was as fasting blood sugar (FBS) ≥ 110 mg/dL. When those with APOA5 -1131 T/T or 553 G/G were defined as references, those with APOA5 -1131 T/C, C/C or 553 G/T, T/T demonstrated significantly elevated risk of dyslipidemia (age- and sex-adjusted odds ratio: 1.77 [95% confidence interval:1.39-2.27], 3.35 [2.41-4.65], 2.23 [1.64-3.02] and 13.78 [3.44-55.18], respectively). Evaluation of FTG, HDL-C or FBS levels according to the genotype revealed that FTG and HDL-C levels were significantly associated with the APOA5 T-1131C and G553T polymorphisms, FTG with the GCKR rs780094 and rs1260326 polymorphisms, and FBS with the GCKR rs780094 and rs1260326 polymorphisms. Moreover, a significant positive interaction between APOA5 553 G/T+T/T genotypes and fat intake ≥ 25% of total energy for the risk of dyslipidemia was observed. Our cross-sectional study confirmed the essential roles of the polymorphisms of the APOA5, GCK and GCKR in the lipid or glucose metabolism disorders, and suggested the importance of fat intake control in the individualized prevention of dyslipidemia.

Pro-/anti-inflammatory cytokine gene polymorphisms and chronic kidney disease: a cross-sectional study.

BACKGROUND: The aim of this study was to explore the associations between common potential functional promoter polymorphisms in pro-/anti-inflammatory cytokine genes and kidney function/chronic kidney disease (CKD) prevalence in a large Japanese population. METHODS: A total of 3,323 subjects aged 35-69 were genotyped for all 10 single nucleotide polymorphisms (SNPs) in the promoter regions of candidate genes with minor allele frequencies of > 0.100 in Japanese populations. The estimated glomerular filtration rate (eGFR) and CKD prevalence (eGFR < 60 ml/min/1.73 m2) of the subjects were compared among the genotypes. RESULTS: A higher eGFR and lower prevalence of CKD were observed for the homozygous variants of IL4 -33CC (high IL-4 [anti-inflammatory cytokine]-producing genotype) and IL6 -572GG (low IL-6 [pro-inflammatory cytokine]-producing genotype). Subjects with IL4 CC + IL6 GG showed the highest mean eGFR (79.1 ml/min/1.73 m2) and lowest CKD prevalence (0.0%), while subjects carrying IL4 TT + IL6 CC showed the lowest mean eGFR (73.4 ml/min/1.73 m2) and highest CKD prevalence (17.9%). CONCLUSIONS: The functional promoter polymorphisms IL4 T-33C (rs2070874) and IL6 C-572G (rs1800796), which are the only SNPs that affect the IL-4 and IL-6 levels in Japanese subjects, were associated with kidney function and CKD prevalence in a large Japanese population.

Association between KLK3 rs2735839 G/A polymorphism and serum PSA levels in Japanese men.

OBJECTIVES: To clarify the association of kallikrein-related peptidase 3 (KLK3) rs2735839 G/A polymorphism with serum prostate-specific antigen (PSA) levels in Japanese men. METHODS: Subjects were participants of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study who visited the Seirei Preventive Health Care Center in Shizuoka, Japan. Among the 5,040 individuals aged 35-69 years who were enrolled in 2006-2007, serum PSA data were available for 2,323 male subjects without a past history of prostate cancer. The diagnostic criteria for PSA positivity was PSA ≥ 4.0 ng/ml. Genotyping of the KLK3 polymorphism was conducted by the polymerase chain reaction with the confronting two-pair primers (PCR-CTPP) method. RESULTS: The mean ± SD of PSA levels (mg/dl) were 1.54 ± 1.73 for those with KLK3 rs2735839 G/G genotype, 1.34 ± 1.33 for G/A, and 1.20 ± 1.23 for A/A, which was significantly different (p < 0.0001). The age-adjusted odds ratios of PSA test positivity were 0.62 (95% confidence interval 0.41-0.94) for those with G/A + A/A relative to those with G/G. CONCLUSIONS: The present study revealed that the KLK3 rs2735839 G allele was significantly associated with higher serum PSA levels also in Japanese.

Pilot study on the effects of a 1-day sleep education program: influence on sleep of stopping alcohol intake at bedtime.

The aim of this pilot study was to evaluate whether sleep was improved by a 1-day sleep education program in an occupational setting and whether stopping alcohol intake at bedtime might influence sleep. Subjects were 40 high school employees. The sleep education program lasted 4.5 hours and consisted of sleep science information, and sleep hygiene education including the risk of sleep related breathing disorder resulting from alcohol intake. Sleep conditions were evaluated by self-administered questionnaires at baseline and approximately 1 month later. The mean the Epworth Sleepiness Scale (ESS) score was significantly decreased by 1.2 points (P = 0.04), while the mean sleep duration was significantly decreased by 10 minutes (P = 0.02). Shortened sleep duration coincided with a decrease in sleepiness. This may indicate an improvement in sleep quality. The percentage of habitual alcohol intake at bedtime was significantly decreased (from 38.5% (15/39) to 20.5% (8/39), P = 0.04). Subjects who stopped alcohol intake at bedtime (n = 8) received the most benefit, with decreased scores of ESS and Insomnia Severity Index (ISI), although the reductions were not significant. This education program offers the possibility of improving sleep conditions among the general population, especially in those who cease habitual alcohol intake at bedtime. Further larger, randomized, controlled studies are warranted.

Association of obesity and diabetes with serum prostate-specific antigen levels in Japanese males.

Patients with diabetes have been reported to be at an increased risk for cancers of the pancreas, liver, and colon; however, recent studies have suggested that men with diabetes are at a decreased risk for prostate cancer. Previous studies have found that obese men have lower serum prostate-specific antigen (PSA) concentrations than do non-obese men. Further understanding of how obesity and diabetes affect the PSA concentration may improve our ability to detect clinically relevant prostate tumors. This study examined the relationships among serum PSA level, obesity, and diabetes in apparently healthy Japanese males. We analyzed the baseline data from 2,172 Japanese males (age, 56.8 +/- 6.1 years [mean +/- SD]) who participated in the Japan Multi-Institutional Collaborative Cohort Study. Diabetes was defined as the presence of both a hemoglobin A1c (JDS) of > or = 6.1% and a fasting plasma glucose level of > or = 126 mg/dL, or a positive medical history. After adjusting for age, the PSA levels were elevated among males with a higher normal BMI (ranging from 23.0 to 24.9) and lowered among men with a BMI of > or = 25.0. In the stratified analysis, these significant differences in BMI categories were absent among diabetics. The mean PSA levels were significantly lower in diabetics than in non-diabetics among subjects aged 60 and over. Our findings suggest that the pre-overweight men had increased PSA levels, and the diabetes was associated with a reduction of PSA levels in elderly.

Prevalence of Helicobacter pylori infection measured with urinary antibody in an urban area of Japan, 2008-2010.

Helicobacter pylori (H. pylori) has expanded to infect about half the world's population. Although there were many studies on the prevalence of H. pylori infection for defined areas in the 1990s throughout the world, there were only limited sources tracking its latest prevalence among large populations. In the present study, we estimated the prevalence of H. pylori among the inhabitants of Nagoya, an urban area of Japan. Study subjects were 5167 participants (1467 males and 3700 females) aged 35 to 69 years from the Daiko Study, a part of the Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study). A urinary anti-H. pylori antibody was used to detect H. pylori infection. The history of eradication treatments for H. pylori infection was obtained using self-administered questionnaires. The prevalence detected by the urinary test included 19.6% (95% confidence interval; 16.8-22.6%) for those aged 35-39 years, 25.8% (23.5-28.2%) for 40-49 years, 39.4% (36.8-42.1%) for 50-59 years, 50.3% (47.8-52.7%) for 60-69 years, and 36.4% (35.1-37.7%). Among 5167 participants, 266 (5.1%) stated that they had received an eradication treatment. Since 167 subjects with negative urinary tests replied that they had been seropositive for H. pylori in the past, they were included among the ever-infected inhabitant group. Consequently, the overall rate of those with a history of persistent infection was 39.6% (38.3-40.9%). The prevalence of H. pylori infection observed in Nagoya seemed to be lower than the corresponding prevalence reported in other studies of Japan. That lower rate might be due to the reduced exposure from improved urban sanitary conditions.

Renal hyperfiltration in prediabetes confirmed by fasting plasma glucose and hemoglobin A1c.

BACKGROUND: The aim of the study was to confirm that glomerular hyperfiltration, an early and reversible stage of kidney damage, is associated in patients with prediabetes and prehypertension. METHODS: In total, 5003 people aged between 35 and 69 years who had participated in the Shizuoka part of the Japan Multi-Institutional Collaborative Cohort (J-MICC) study took part in the study. Prevalence of hyperfiltration [the estimated glomerular filtration rate (eGFR) above the age- /sex-specific 95th percentile] was compared among different stages of prediabetes [fasting plasma glucose (FPG) < 100, 100-109, 110-125, and ≥126 mg/dL; and/or hemoglobin A1c (HbA1c) < 5.7, 5.7-6.0, 6.1-6.4 and ≥6.5% for no prediabetes, stage 1 prediabetes, stage 2 prediabetes, and overt diabetes, respectively] and prehypertension (blood pressure <120/80, 120-129/80-84, 130-139/85-89, and ≥140/90 mmHg for no prehypertension, stage 1 prehypertension, stage 2 prehypertension, and overt hypertension, respectively). RESULTS: The prevalence of hyperfiltration increased with increasing stages of prediabetes (odds ratios: 1.25, 1.68, and 2.37 using FPG, and 1.26, 2.15, and 2.45 using HbA1c for stage 1 prediabetes, stage 2 prediabetes, and diabetes, respectively, relative to no prediabetes). Prehypertension, however, was not associated with hyperfiltration. CONCLUSION: The results confirmed that the prevalence of glomerular hyperfiltration increased with increasing stages (i.e., worsening) of prediabetes. Because both FPG and HbA1c showed similar association with hyperfiltration, either of these can be used to identify subjects who are at increased risk of nephropathy. Therefore, the functioning of kidneys should be monitored in subjects with prediabetes. Prompt treatment of hyperglycemia is necessary in subjects with hyperfiltration to prevent it to cause nephropathy.