HuBit Genomix Research Institute

Tokyo, Japan

HuBit Genomix Research Institute

Tokyo, Japan
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Konta T.,Yamagata University | Takasaki S.,Yamagata University | Ichikawa K.,Yamagata University | Emi M.,HuBit Genomix Research Institute | And 10 more authors.
Journal of Human Genetics | Year: 2010

Nephronophthisis (NPHP) 4 gene coding nephrocystin-4 is involved in the development of renal tubules and its congenital mutations cause juvenile end-stage renal disease, NPHP. To investigate the association between single-point single-nucleotide polymorphism (SNP) of NPHP4 gene and renal function, we conducted a cross-sectional study in Japanese population. The subjects of this study were non-diabetic general population consisting of 2604 individuals >40 years in Takahata town, Japan. We genotyped 11 SNPs within NPHP4 gene that displayed frequent minor allele frequencies (>0.1) in Japanese general population. Among 11 SNPs in NPHP4 gene, only rs1287637 that induces amino acid substitution (A (Gln)/T (Leu)), located in the acceptor site of exon 21, showed a significant association with estimated glomerular filtration rate (eGFR; T/T: 81.3±15.6 (n=1886), A/T: 82.0±15.5 (n=652) and A/A: 87.4±21.4 ml min -1 per 1.73m 2 (n=66); mean±s.d., P=0.006). This SNP was not in linkage disequilibrium with the surrounding SNPs. The multivariate analysis adjusted with possible confounders showed that the A/T+T/T genotype of rs1287637 was independently associated with reduced renal function (eGFR <90 ml min -1 per 1.73m 2; odds ratio (OR) 1.75, 95% confidence interval (CI) 1.05-2.94, P=0.033). These results indicate the novel and independent association between single-point SNP rs1287637 in NPHP4 gene and renal function in non-diabetic Japanese population. © 2010 The Japan Society of Human Genetics All rights reserved.

Karasawa S.,Yamagata University | Daimon M.,Yamagata University | Sasaki S.,University of Tokyo | Toriyama S.,Yamagata University | And 12 more authors.
Endocrine Journal | Year: 2010

The association of the FTO gene polymorphism, rs9939609, with obesity was examined using the population of the Takahata study (n (M/F): 2,639 (1,168 / 1,470); age: 63.0 ± 10.2 years), a Japanese community-based study. The effects of lifestyle-related factors, including nutritional intake and physical activities, on the association were also examined. Body mass index (BMI) was significantly associated with the FTO gene polymorphism (p<0.001). A case-control association study of the FTO gene polymorphism with obesity using multiple logistic regression analysis showed a significant association of the genotype AA (odds ratio, 1.53 [95% confidential interval, 1.04-2.24]) after adjustment for age and gender. Analysis to examine the differences in lifestyle-related factors among the genotype groups showed a significant difference in the energy expenditure for moderate to high-intensity physical activity (PA) (≥ 3.0 METs) (p=0.012) with a significant decrease toward the genotype AA (p=0.027). The effect of energy expenditure for moderate to high-intensity PA on the association of the polymorphism with obesity was then examined using study groups stratified based on the energy expenditure for moderate to high-intensity PA (Low-PA and High-PA). The BMI was significantly higher in the genotype AA in the Low-PA group (p=0.016) but not in the High-PA group (p=0.103). Furthermore, the genotype AA was significantly associated with obesity (odds ratio, 2.39 [95% confidential interval, 1.19-4.80]) in the Low-PA group but not in the High-PA group (p=0.650). The FTO gene, rs9939609, was associated with obesity, and the association was evident in subjects with low-PA, suggesting a PA-dependent association.

Daimon M.,Yamagata University | Oizumi T.,Yamagata University | Karasawa S.,Yamagata University | Kaino W.,Yamagata University | And 11 more authors.
Metabolism: Clinical and Experimental | Year: 2011

The association of the clusterin (CLU) gene polymorphism (single nucleotide polymorphisms [SNPs] 1-4: rs1532278, rs1532277, rs2279590, and rs2279591, respectively) with type 2 diabetes mellitus was examined using a population of the Funagata study (n [male-female] = 1631 [741:884]; age, 62.0 ± 12.1 years), a Japanese community-based study. Single nucleotide polymorphisms 1 to 3 were significantly associated with hemoglobin A1c levels (P = .0154, .0021, and .0006, respectively) and diabetes (.0310, .0170, and .0021, respectively). A case-control association study of SNP 3 with diabetes by multiple logistic regression analysis showed a significant association of genotype AA (the at-risk genotype) with an odds ratio (OR) of 2.33 (P = .0039) independently of age and sex. The association was marginally validated by a study with another Japanese community-based sample, the Takahata Study (n [male-female] = 2.948 [1333:1615]; age, 63.0 ± 10.2 years) (OR, 1.59; P = .0595; χ2 P = .0264). When the 2 samples were combined, the association became more significant (OR, 1.75; P = .0025). In subjects with the non-at-risk genotypes, the insulin resistance index-homeostasis model assessment of insulin resistance (HOMA-R)-increased significantly (P < .0001) and the insulin secretion index-HOMA-β-appeared to decrease (P = .1803 and .0097, respectively, for the genotypes AG and GG) as the glucose tolerance progressed toward diabetes (normal glucose tolerance to glucose intolerance to diabetes). However, in subjects with the at-risk genotype, HOMA-R and HOMA-β showed a significant increase already in the subjects with normal glucose tolerance (P = .0239 and .0305, respectively); and as the glucose tolerance progressed toward diabetes, HOMA-R stayed approximately the same, whereas HOMA-β decreased significantly (P = .0332). The CLU gene was associated with diabetes, probably through an increase in insulin resistance primarily and through an impairment of insulin secretion secondarily. © 2011 Elsevier Inc. All rights reserved.

Daimon M.,Yamagata University | Sato H.,Yamagata University | Sato H.,HuBit Genomix Research Institute | Kaino W.,Yamagata University | And 11 more authors.
Journal of Human Hypertension | Year: 2013

Association of the C825T G-protein β3 subunit (GNB3) gene polymorphism with cardiovascular disease (CVD) incidence was examined in a population-based longitudinal study of the Japanese individuals. The incidence of CVD (stroke and coronary heart disease (CHD)) was assessed in a cohort population (n=1524) consisting of participants of the 2001-2005 Funagata study through March 2008. Cumulative incidences according to genotype were compared with the Kaplan-Meier product-limit method. During the follow-up, 78 subjects experienced a CVD event (stroke: n=54; CHD: n=30; both consecutively: n=6). At the end of the follow-up (longest and median follow-up periods: 81 and 68 months, respectively), the cumulative incidence of CVD for the TT genotype was significantly higher than that of the C-carriers (0.077 vs 0.042, P=0.004). Blood pressures and the prevalence of hypertension were not different between the genotypes. Cox's proportional hazard analysis showed that the TT genotype is a significant risk factor for CVD (hazard ratio (HR)=1.82 (95% confidence interval (CI) 1.14-2.89); P=0.012) and stroke (HR=1.76 (95% CI: 1.01-3.07); P=0.048) incidences after adjustment for age, sex, hypertension, hyperlipidemia, diabetes, alcohol drinking and smoking at baseline. The TT genotype of the C825T GNB3 gene polymorphism was found to be a significant risk factor for the incidence of CVD and stroke independent of hypertension and other established CVD risk factors in a Japanese population. © 2013 Macmillan Publishers Limited All rights reserved.

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