Peroxisome Proliferator–Activated Receptor γ Polymorphism Pro12Ala Is Associated With Nephropathy in Type 2 Diabetes

Abstract

OBJECTIVEInsulin resistance plays a part in diabetic nephropathy (DN). The association between the peroxisome proliferator–activated receptor γ Pro to Ala alteration at codon 12 (Pro12Ala) polymorphism and the risk of insulin resistance has been confirmed. The association between the polymorphism and DN risk has also been widely studied recently, but no consensus was available up to now.RESEARCH DESIGN AND METHODSA systematic search of electronic databases (MEDLINE, Embase, and China National Knowledge Infrastructure) and reference lists of relevant articles was carried out, and then 18 case-control studies involving 3,361 DN cases and 5,825 control subjects were identified.RESULTSIn the overall analysis, the Ala12 variant was observed to be significantly associated with decreased DN risk (odds ratio 0.76 [95% CI 0.61–0.93]). Some evidence of heterogeneity among the included studies was detected, which could be explained by the difference of ethnicity and stage of DN. Subgroup analyses stratified by ethnicity and stage of DN were performed, and results indicated the Pro12Ala polymorphism was associated with the risk of DN in Caucasians but no similar association was observed in Asians. Additionally, we observed that Ala12 was associated with decreased risk of albuminuria. With only a few of subjects were available, we failed to detect statistically significant association between the polymorphism and end-stage renal disease (ESRD).CONCLUSIONSOur results indicated that the Ala12 variant is a significantly protective factor for DN. Future research should focus on the effect of Pro12Ala polymorphism on ESRD and gathering data of Africans.

The association between lipid metabolism gene polymorphisms and nephropathy in type 2 diabetes: a meta-analysis

“…These results highly suggest a protective functional role of PPARγ in diabetic nephropathy. In agreement with this conclusion, numerous studies containing a meta-analysis of 18 studies involving 3,361 patients convincingly demonstrated a significant protective effect against for T2DN [38]. And their results indicated rs1801282 C>G polymorphism was associated with the reduced risk of T2DN in Caucasians but no similar association was observed in Asians, but our study have found that the C>G polymorphism in rs1801282 showed a significant protective role for T2DN in both Asians and Caucasians.…”

The association between the PPARγ2 Pro12Ala polymorphism and nephropathy susceptibility in type 2 diabetes: a meta-analysis based on 9,176 subjects

“…18 publications addressing the association between PPARγ2 Pro12Ala polymorphism and DN risk were preliminarily eligible [8,9,17-30]. Table 1 presents the main characteristics of these studies.…”

The Pro12Ala Polymorphism in the Peroxisome Proliferator-Activated Receptor Gamma-2 Gene (PPARγ2) Is Associated with Increased Risk of Coronary Artery Disease: A Meta-Analysis

“…The most common gene polymorphism in human PPARγ2 gene is cytosine-guanine exchange in exon B (codon12) which results proline to alanine (Pro12Ala) substitution in the protein [6].The Pro12Ala polymorphism was first identified by Yen et al [7] in 1997 and regarded to reduce transcriptional activity of PPARγ2 [8], resulting in lower transcription levels of target genes [9],including tumor necrosis factor α ( TNF α ), leptin, resistin, adiponectin, and plasminogen activator in hibitor-1( PAI - 1 ), which play important roles in the process of inflammation and atherosclerosis. There are evidences that the resulting mutant transcription factor profoundly affects the energy metabolism and energy balance and is associated with the risks of atherogenesis [10]–[12] and diabetes [13], [14]. In addition, the Pro12Ala polymorphism was regarded to change the response of synthetic PPARγ agonists– thiazolidinediones (TZDs) treatment [15], which seemed to improve the insulin resistance [16] and limit atherosclerosis development [17].…”