Dataset Information

Polymorphisms in PPAR Genes (PPARD, PPARG, and PPARGC1A) and the Risk of Chronic Kidney Disease in Japanese: Cross-Sectional Data from the J-MICC Study.

ABSTRACT: Chronic kidney disease (CKD) is well known as a strong risk factor for both end stage renal disease and cardiovascular disease. To clarify the association of polymorphisms in the PPAR genes (PPARD, PPARG, and PPARGC1A) with the risk of CKD in Japanese, we examined this association among the Japanese subjects using the cross-sectional data of J-MICC (Japan Multi-Institutional Collaborative Cohort) Study. The subjects for this analysis were 3,285 men and women, aged 35-69 years, selected from J-MICC Study participants; genotyping was conducted by multiplex polymerase chain reaction-based Invader assay. The prevalence of CKD was determined for CKD stages 3-5 (defined as eGFR

SUBMITTER: Hishida A

PROVIDER: S-EPMC3830885 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Polymorphisms in PPAR Genes (PPARD, PPARG, and PPARGC1A) and the Risk of Chronic Kidney Disease in Japanese: Cross-Sectional Data from the J-MICC Study.

Hishida Asahi A Wakai Kenji K Naito Mariko M Tamura Takashi T Kawai Sayo S Hamajima Nobuyuki N Oze Isao I Imaizumi Takeshi T Turin Tanvir Chowdhury TC Suzuki Sadao S Kheradmand Motahare M Mikami Haruo H Ohnaka Keizo K Watanabe Yoshiyuki Y Arisawa Kokichi K Kubo Michiaki M Tanaka Hideo H

PPAR research 20131107

Chronic kidney disease (CKD) is well known as a strong risk factor for both end stage renal disease and cardiovascular disease. To clarify the association of polymorphisms in the PPAR genes (PPARD, PPARG, and PPARGC1A) with the risk of CKD in Japanese, we examined this association among the Japanese subjects using the cross-sectional data of J-MICC (Japan Multi-Institutional Collaborative Cohort) Study. The subjects for this analysis were 3,285 men and women, aged 35-69 years, selected from J-MI ...[more]

PMID: 24288525

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Project description:Chronic kidney disease (CKD) is known to be one of the causes of cardiovascular disease and end-stage renal disease. Among the several treatable risk factors of CKD, that of dyslipidemia is relatively controversial. To clarify the association of polymorphisms in genes involved in lipid metabolism with the risk of CKD in the Japanese population, we used cross-sectional data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study.A total of 3,268 men and women, aged 35-69 years, were selected from J-MICC Study participants for inclusion in this study. Twenty-eight candidate single nucleotide polymorphisms (SNPs) were selected in 17 genes associated with the risk of lipid metabolism disorders, and genotyping of the subjects was conducted using the multiplex PCR-based invader assay. The prevalence of CKD was determined for stages 3-5 (defined as estimated glomerular filtration rate <60 ml/min/1.73 m2).Logistic regression analysis revealed that SNPs APOA5 T?-?1131C (rs662799), APOA5 T1259C (rs2266788), TOMM40 A/G (rs157580), and CETP TaqIB (rs708272) were significantly associated with CKD risk in those individuals genotyped, with age- and sex-adjusted odds ratios (ORs) per minor allele (and 95% confidence intervals (CIs)) of OR 1.22 (95% CI: 1.06-1.39), 1.19 (1.03-1.37), 1.27 (1.12-1.45), and 0.81 (0.71-0.92), respectively. Analysis of the gene-environment interaction revealed that body mass index (BMI) was a significant effect modifier for APOA5 T?-?1131C (rs662799) and a marginally significant effect modifier for APOA5 T/C (rs2266788), with the interaction between BMI ?30 and individuals with at least one minor allele of each genotype of OR 10.43 (95% CI: 1.29-84.19) and 3.36 (0.87-13.01), respectively.Four polymorphisms in APOA5, TOMM40, and CETP were shown to be significantly associated with CKD risk, and a significant interaction between the two APOA5 SNPs and BMI on CKD risk was also demonstrated. This suggests the future possibility of personalized risk estimation for this life-limiting disease.

Project description:Pediatric obesity presents a multifactorial etiology, which involves genetic traits as well, including single nucleotide polymorphisms. The aim of the study is to investigate the contribution of PPARG gene polymorphisms (namely Pro12Ala rs1801282, His447His rs3856806, and Pro115Gln rs1800571) and PPARGC1A rs8192678 SNP on the anthropometric and metabolic parameters in a population of Romanian children. We conducted a cross-sectional study of 295 Caucasian children, divided according to the body mass index (BMI) z-score into the study (obese and overweight) group of 130 children and the control (normoponderal) group of 165 children. Anthropometric parameters were greater in the obese and overweight population as opposed to controls, with significant differences (p < 0.01) found for the weight (2.77 ± 1.54 SD vs. -0.04 ± 1.15 SD), body mass index (BMI) (2.28 ± 0.97 SD vs. -0.18 ± 1.19 SD), mid-upper arm circumference (MUAC) (4.59 ± 2.28 SD vs. 0.28 ± 3.45 SD), tricipital skin-fold (TSF) (3.31 ± 3.09 SD vs. 0.62 ± 7.28 SD) and waist-to-height ratio (WHtR) (0.61 ± 1.51 SD vs. -0.35 ± 1.35 SD) z-scores. Moreover, triglyceride values were higher in the study group (118.70 ± 71.99 SD vs. 77.09 ± 37.39 SD). No significant difference in the allele and genotype distribution of investigates gene polymorphisms was observed between the studied groups (p > 0.05). PPARG (rs1801282, rs3856806, and rs1800571) were not associated with demographic, anthropometric, and laboratory parameters. However, PPARGC1A rs8192678 CC genotype was associated with TSF z-score (p = 0.03), whereas total and LDL cholesterol levels were significantly higher among TT homozygotes (p < 0.01). Our data suggest that PPARG (rs1801282, rs3856806, and rs1800571) and PPARGC1A (rs8192678) gene polymorphisms were not associated with childhood and adolescence overweight and obesity. The present study identified a significant increase in fasting glucose levels, triglyceride, albumin, and ALT levels in children with excess weight, as well as expected important upward variation of anthropometric parameters (BMI, MUAC, TSF z-scores).

Project description:Several single nucleotide polymorphisms (SNPs) have been implicated in the predisposition to chronic kidney disease (CKD). Atherosclerotic disease is deeply involved in the incidence of CKD; however, whether SNPs related to arteriosclerosis are involved in CKD remains unclear. This study aimed to identify SNPs associated with CKD and to examine whether risk allele accumulation is associated with CKD.We conducted a cross-sectional study using data of 4814 male workers to examine the association between estimated glomerular filtration rate (eGFR) and 59 candidate polymorphisms (17 CKD, 42 atherosclerotic diseases). We defined the genetic risk score (GRS) as the total number of risk alleles that showed a significant association in this analysis and examined the relationship with CKD (eGFR < 60 ml/min/1.73m2). Multivariate logistic regression, discrimination by area under the receiver operating characteristic curve, integrated discrimination improvement (IDI), and category-free net reclassification improvement (cNRI) were evaluated.In total, 432 participants were categorized as having CKD. We found eight candidate SNPs with P value < 0.05 (CX3CR1 rs3732379, SHROOM3 rs17319721, MTP rs1800591, PIP5K1B rs4744712, APOA5 rs662799, BRAP rs3782886, SPATA5L1 rs2467853, and MCP1 rs1024611) in the multivariate linear regression adjusted for age, body mass index, systolic blood pressure, and fasting blood glucose. Among these eight SNPs, BRAP rs3782886 and SPATA5L1 rs2467853 were significantly associated with eGFR (false discovery rate < 0.05). GRS was significantly associated with CKD (odds ratio, 1.17; 95% confidence interval, 1.09-1.26). C-statisics improved from 0.775 to 0.780 but showed no statistical significance. However, adding GRS significantly improved IDI and cNRI (0.0057, P = 0.0028, and 0.212, P < 0.001, respectively).After adjustment for clinical factors, kidney function was associated with BRAP rs3782886 and SPATA5L1 rs2467853 and the GRS for CKD that we developed was associated CKD.

Dataset Information

Polymorphisms in PPAR Genes (PPARD, PPARG, and PPARGC1A) and the Risk of Chronic Kidney Disease in Japanese: Cross-Sectional Data from the J-MICC Study.

Publications

Polymorphisms in PPAR Genes (PPARD, PPARG, and PPARGC1A) and the Risk of Chronic Kidney Disease in Japanese: Cross-Sectional Data from the J-MICC Study.

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