Association of single-nucleotide polymorphisms in the &ITRAGE&IT gene and its gene- environment interactions with diabetic nephropathy in Chinese patients with type 2 diabetes

Aims: To investigate the association of several single nucleotide polymorphisms (SNPs) within RAGE gene and additional gene- smoking interaction with diabetic nephropathy (DN) risk in Chinese patients with type 2 diabetes mellitus (T2DM). Methods: A total of 865 participants (570 males, 295 females) were selected, including 430 T2DM complicated DN patients and 435 controls (T2DM patients without DN). Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among SNPs and smoking. Logistic regression was performed to investigate impact of 4 SNPs within RAGE gene, additional gene-smoking interaction on DN risk. Results: DN risk was significantly higher in carriers with the C allele of rs1800625 than those with TT genotype, adjusted OR (95%CI) = 1.57 (1.16-2.17), and higher in carriers with the T allele of rs184003 than those with GG genotype, adjusted OR (95%CI) = 1.64 (1.21-2.12). GMDR model indicated a significant two-locus model (p = 0.0010) involving rs1800625 and smoking, the cross-validation consistency of this two- locus model was 10/ 10, and the testing accuracy was 60.72%. We also conducted stratified analysis for the significant models in the GMDR analysis by using logistic regression. We found that current smokers with rs1800625- TC or CC genotype have the highest DN risk, compared with never-smokers with rs1800625- TT genotype, OR (95%CI) = 2.92 (1.94 -3.96), after covariates adjustment. Conclusions: We found that the C allele of rs1800625 and the T allele of rs184003 within RAGE gene, interaction between rs1800625 and smoking were all associated with increased DN risk.