Abstract: Objective To investigate the association between glucagon-like peptide-1 receptor (GLP-1R) gene polymorphism (rs2268641) and the incidence of diabetic nephropathy (DN) in patients with type 2 diabetes mellitus (T2DM). Methods A total of 490 T2DM patients with or without DN were included in this project. GLP-1R genetic polymorphisms were genotyped with TaqMan allelic discrimination. Results The C allele of rs2268641 was significantly associated with DN in T2DM patients. As compare to urinary albumin excretion rate(UAER) among genotypes, CC homozygote had a higher level of UAER than CT heterozygous (P＜0.01) and TT homozygote(P＜0.05) respectively. CC homozygote had a higher level of UAER than the carriers of the T allele(P＜0.05). Univariate logistic regression analysis showed that CC homozygote had higher odds for DN than CT heterozygote (OR:1.715, 95% CI=1.058-2.778, P＜0.05), even after adjustment for age, gender, family history, FBG and HbA1c (OR:1.781, 95% CI=1.076-2.947, P＜0.05). Moreover, the CC homozygote had higher odds for DN than the carriers of the T allele before (OR:1.585, 95% CI=1.013-2.481, P＜0.05) and after adjustment (OR:1.660, 95% CI=1.040-2.650, P＜0.05). Conclusions GLP-1R gene variants, especially the C allele of rs2268641 increase the risk of DN in Chinese T2DM patients.

Key words: type 2 diabetes mellitus, diabetic nephropathy, glucagon-like peptide-1 receptor(GLP-1R), genetic polymorphism