Association between PPARG Pro۱۲Ala polymorphism and diabetic nephropathy risk; an updated meta-analysis of ۲۷ studies

Diabetic nephropathy (DN) is one major complication of hyperglycemia in diabetes patients. The relationship between peroxisome proliferator-activated receptors gamma (PPARG) gene rs۱۸۰۱۲۸۲ (Pro۱۲Ala) polymorphism and the risk of DN has been investigated previously. However, the results were conflicting. In this study, we assessed whether PPARG gene rs۱۸۰۱۲۸۲ polymorphism is associated with the risk of DN by meta-analysis. We searched in PubMed, Science Direct and Google Scholar databases using a combination of terms of ‘Diabetic nephropathy’, ‘peroxisome proliferator activated receptor gamma’, ‘PPARG’, ‘Pro۱۲Ala polymorphism’ and rs۱۸۰۱۲۸۲” between January ۲۰۰۱ and July ۲۰۱۷. Twenty-seven original studies involving ۵۴۴۳ cases and ۷۲۶۲ controls were analysed. Studies conducted in several countries in Europe and North America were assigned to the Caucasian ethnic group and countries in South, East and South East Asia were assigned to an Asian ethnic group. Pooled odds ratios (ORs) and ۹۵% confidence intervals (CIs) were calculated. The heterogeneity of the included studies was examined with Cochran Q and I² statistics. Begg’s rank correlation test and Egger’s linear regression test were used to assess the publication bias. Our meta-analysis indicated that the PPARG Ala۱۲ allele carriers reduced the DN risk in study populations (P < ۰.۰۰۱, OR = ۰.۷۶۰, ۹۵% CI = ۰.۶۷۷-۰.۸۵۳). Although there is moderate heterogeneity between studies (Pheterogeneity < ۰.۰۰۷, Q= ۴۷.۰, df = ۲۶, I-squared = ۴۴.۷%), publication bias was not seen. However, subgroup analyses showed that in Asian populations, a significant association was not found between the PPARG Pro۱۲Ala and DN risk (P = ۰.۱۳۳, OR = ۰.۷۹۶, ۹۵% CI = ۰.۵۹۱-۱.۰۷۲). The PPARG Pro۱۲Ala polymorphism is a genetic risk factor for DN in Caucasian populations and no conclusion of a causal relationship can be drawn from the available data.

کلیدواژه ها:

PPAR-gamma ، Pro۱۲Ala ، Diabetic Nephropathy ، Meta-analysis ، Asians ، Caucasians