Association Analysis Of Promoter Region Polymorphisms Of Receptor Of Advanced Glycation End Products(RAGE) Gene In Han People Of Wuxi Area With Diabetic Retinopathy

Objective Diabetic retinopathy(DR) is one of the main complications in type 2 dibetic patients and also it could always lead to blindness. Previous studies showed that progression of DR was not only associated with blood glucose control and duration, but genetic factors also played significant roles. Recent studies reveal that the receptor for advanced glycation end products (RAGE) plays an important role in T2DM microvascular lesions. This article aims to investigate the correlation between the RAGE -374T>A,-429T>C gene polymorphisms and DR in type 2 diabetes mellitus.Methods Using case -control study method, the promoter region polymorphisms of RAGE gene were amplified by PCR and sequenced in 120 normal control subjects and 185 patients with type 2 diabetes mellitus, including 92 subjects with DR and 93 subjects with non-diabetic retinopathy (NDR). The frequencies of RAGE genotype, allele and biochemical criterion among those groups were compared using χ2 test and an independent samples t test.Results For -374T>A, all of the three groups obtain three kinds of genetypes, TT, TA and AA. For -429T>C, all of the three groups also obtain three kinds of genetypes, TT, TC and CC. Each genotype frequencies and allele frequencies in both of two gene locus are consistent with Hardy-Weinberg(P>0.05). This means that the selected population should be in the genetic equilibrium state and has the very good representative. For the -374T>A, TA+AA genotype frequencies and A allele frequencies in NDR group and normal control group revealed no significant differences(P>0.05). While the TA+AA genotype frequencies and A allele frequencies in DR group were higher than in NDR group, there were statistical significant differences (χ2=4.985, P=0.026; χ2=5.951, P=0.015). For the -429T>C, TC+CC genotype frequencies and C allele frequencies in NDR group and normal control group showed no significant differences (P>0.05). While the TC+CC genotype frequencies and C allele frequencies in DR group were higher than in NDR group,there were statistical significant differences(χ2=7.938, P=0.005;χ2=7.317, P=0.007).Single factor logistic regression analysis showed that for -374T>A, the A allele should be associated with DR (OR=1.934,95%CI:1.132-3.303). For -429T>C, the C allele should also be related with DR (OR=2.085,95%CI:1.216-3.574).The disease course in DR group was significantly longer than that in NDR group (t=2.25, P<0.05). Other biochemical criterions in both groups were not significant different(P>0.05).Conclusion ①RAGE -374T>A、-429T>C gene polymorphisms may be associated with the development of DR, and A allele、C allele may be the risk factor for people in Wuxi. ②With longer duration of diabetes, the incidence of diabetic retinopathy was increased(t=2.25, P<0.05).