Study On The Association Between Polymorphisms -374T/A And -429T/C In Receptor For Advanced Glucation End Products (RAGE) Gene And Type 2 Diabetes Melltus With Nephropathy Or Retinopathy

Objective Study on the association of polymorphisms -374T/A and -429T/C in receptor for advanced glucation end products (RAGE) gene with type 2 diabetic nephropathy and retinopathy. Methods The genotypes of RAGE gene polymorphisms: -429T/C, -374T/A and (-407/345)63-bpI/D were determined by polymerase chain reaction-restriction fragment-length polymorphism analysis in 496 cases patients of type 2 diabetes melltus (T2DM),79 cases impaired glucose tolerance patients(IGT), 243 cases of normal glucose tolerance (NGT) in Chinese people in Anhui region. Type 2 diabetic patients were divided by urine albumium excretion rate into four groups which are consisted of normal urine albumium excretion rate group(DN-0),micro-urine albumium excretion rate group(MUDN), clinical diabetic nephropathy group(CDN)and end-stage renal disease group(EDN).We also divided type 2 diabetic patients into three groups defined by examination of direct ophthalmoscopy which consisted of non-diabetic retinopathy(NDR), simple diabetic retinopathy(SDR) and proliferate diabetic retinopathy(PDR).We compared the genotype frequency and allelic frequency among these groups. Results We found that there were no statistically significant differences of genotype frequencies and allelic frequencies of polymorphism -374T/A in RAGE gene among NGT, group IGT and the subgroups of T2DM. There were statistically significant differences of genotype frequencies and allelic frequencies of polymorphism -429T/C in RAGE gene among those subgroups with or without diabetic nephropathy defined by urine albumium excretion rate. The frequencies of genotype TC/CC and ?29C allele in type 2 diabetes mellirus with nephropathy were both lowerthan that without nephropathy. The frequencies of genotype TC/CC and -429C allele in group CDN were lower than other groups. It was showed by multiple logistic regression analysis that there was statistically significant association between genotype TC/CC and clinical diabetic nephropathy. but there were no statistically significant differences genotype frequencies and allelic frequencies of polymorphism among those subgroups with or without diabetic retinopathy. Conclusions These results imply that polymorphism -374T/A in RAGE gene may have no associations with type 2 diabetes with nephropathy or retinopathy . Polymorphism -374T/A in RAGE gene may be associated with diabetic nephropathy, TC/CC genotype and -A29C allele of this polymorphism may play a protective role in the pathogenesis of clinical diabetic nephropathy. Systonic blood pressure(SBP) is a independent risk factor of type 2 diabetic nephropathy. But further studies on larger populations are need to prove these results.