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
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 <？60？ml/min/1.73？m2). Participants with CKD accounted for 17.3% of the study population. When those with PPARD T-842C T/T were defined as reference, those with PPARD T-842C T/C and C/C demonstrated the OR for CKD of 1.26 (95%CI 1.04–1.53) and 1.31 (95%CI 0.83–2.06), respectively. There were no significant associations between the polymorphisms in other PPAR genes and the risk of CKD. The present study found a significantly increased risk of CKD in those with the C allele of PPARD T-842C, which may suggest the possibility of personalized risk estimation of this life-limiting disease in the near future. 1. Introduction Chronic kidney disease (CKD) is recently attracting attention as a leading cause of end-stage renal disease (ESRD) and a potential risk factor for cardiovascular disease (CVD). The prevalence of CKD is increasing over time in Japan, reaching about 22% of the adult population in 2002 [1–4]. Although the prevalence of CKD is shown to be specifically higher in Japan compared to those in other countries [5], it is also reported that about 10–15% of adults are affected by this disease in the developed Western countries [2], suggesting that CKD is becoming a general major public health problem worldwide, making its prevention a pressing universal issue. Meanwhile, metabolic disorders are shown to play an important role in the genesis of CKD mainly through the mechanisms of insulin resistance, resultant hyperinsulinemia, and subsequent increase in plasma renin activity and plasma level of the renal vasoconstrictor angiotensin II [6]. While recent reports suggest that the MetS is an independent predictor of CKD development and progression [7], there are some other possible pathogenic factors causing CKD, such as smoking, hyperuricemia, and homocysteinemia [8]. Peroxisome proliferator-activated receptors (PPARs) are the firstly identified genetic sensor responsive to fatty acid
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