Adiponectin gene (ADIPOQ) polymorphisms correlate with the progression of nephropathy in Taiwanese male patients with type 2 diabetes

Abstract

Aims: Polymorphisms of the ADIPOQ gene were associated with diabetic nephropathy (DN) in case-control studies predominantly among European populations. Gender may modify the ADIPOQ associated risk for DN. We investigated the association of 18 ADIPOQ polymorphisms with DN in a prospective Taiwanese cohort of type 2 diabetes (T2D) and explored whether gender plays a role in this genetic association.

Methods: Selected single nucleotide polymorphisms (SNPs) of ADIPOQ were genotyped in 566 T2D patients with normoalbuminuria at baseline. DN was defined based on urinary albumin-to-creatinine ratio (ACR). The Cox proportional hazard model was used to explore the association of individual SNP to DN events under different genetic models over a 6-year follow-up period. Analyses were further stratified by gender.

Results: In male patients, the adjusted hazard ratios under the recessive models were 1.81 for rs2241766 TT (vs. GT+GG, 95% CI=1.10-2.96, p=0.019) and 1.89 for rs1063537 CC (vs. CT+TT, 95% CI=1.15-3.11, p=0.013). In the Kaplan-Meier survival curve, males carrying rs2241766 TT (vs. GT+GG, p=0.050) and rs1063537 CC (vs. CT+TT, p=0.037) recessive homozygotes also had a reduced nephropathy-free survival rate. SNPs rs2241767 and rs2082940, both in strong correlation with tag SNP rs1063537 (r(2)≥ 0.96), were also associated with DN progression in males. In females, ADIPOQ polymorphisms were not associated with the progression of DN.

Conclusions: ADIPOQ genetic polymorphisms rs2241766 (+45T>G), rs1063537, rs2241767 and rs2082940 were correlated with the progression of DN in Taiwanese male patients with T2D. The role of gender in this ADIPOQ genetic association needs to be further investigated in other populations.

Keywords: ADIPOQ; Diabetic nephropathy; Gender-specific; Polymorphism.