The Impact of Peroxisome Proliferator-Activated Receptor Gamma and Its Interaction with Abdominal Obesity on Diabetic Nephropathy in Chinese Han

Abstract

Background: Several studies have focused on the association between peroxisome proliferators-activated receptor gamma (PPARG) polymorphism and diabetic nephropathy (DN); however, the results of these studies were inconsistent, and until now, no population-based study has focused on the impact of PPARG gene-abdominal obesity interaction on DN risk. The aim of this study was to investigate the impact of PPARG polymorphisms and its interaction with abdominal obesity on DN risk in the Chinese Han population. Methods: A total of 848 patients with type 2 diabetes mellitus, including 420 DN patients and 428 controls were recruited. Generalized multifactor dimensionality reduction (GMDR) and logistic regression model were used to examine the association and interaction between single nucleotide polymorphism and abdominal obesity on DN; OR and 95% CI were calculated. Results: We found a significant association between CG or GG in rs1805192 and increased DN risk. DN risk was higher in the carriers of CG or GG genotype of rs1805192 than those with CC genotype; OR (95% CI) was 1.31 (1.11-1.58). GMDR analysis suggested a significant 2-locus model (p = 0.0107) involving rs1805192 and abdominal obesity, indicating a potential gene-environment interaction between rs1805192 and abdominal obesity. Overall, the 2-locus models had a cross-validation consistency of 10 of 10, and the testing accuracy of 62.17%. Conclusions: Our results support an important association between rs1805192 minor allele (G allele) of PPARG and increased DN risk; the interaction analysis showed a combined effect of interaction between rs1805192 and abdominal obesity on DN risk. The results obtained from this study are meaningful for studies on individualized PPARG agonist in treating DN for different persons, such as abdominal obese or non-abdominal obese subject.