To clarify whether genetic variants of the renin angiotensin system (RAS) contribute to the development of diabetic nephropathy (DN) in the Chinese Methods Totally 173 Chinese subjects of Han nationality from Shanghai were classified into!control, DN ( ) and DN (+) groups The latter was subdivided according to diabetic duration at the onset of DN and the stage of DN Genotyping of five polymorphic sites in four key genes of the RAS: the AGT T174M, AGT M235T and AGTR1 genotypes were determined by PCR/restriction enzyme digestion The insertion/deletion (I/D) and [ACAC]n STR microsatellite polymorphic markers were used for ACE and REN genotyping, respectively Statistical analysis showed comparisons of gene frequencies between any two groups were made with Fisher’s exact test or Chi square test Logistic regression analysis was performed to identify predictors of DN Results The frequencies of ACE DD genotype and ACE D allele were much higher in DN(+) group than in DN( ) group (0 25 vs 0 05, 0 47 vs 0 29, respectively), so were the frequencies of TT genotype and T allele in AGT M235T (0 73 vs 0 54, 0 85 vs 0 68, respectively) DN (+) DUR<5 years group had greatly increased frequencies of AGT M235T allele and ACE DD genotype in comparison with DN( ) group (0 92 vs 0 68 and 0 28 vs 0 05, respectively) Logistic regression analysis further identified these two genes as contributing factors to DN Although AGTR1 and AGT T174M genotyping analysis revealed differences in frequency distribution between DN (+) and DN ( ) or control groups, logistic regression analysis failed to implicate them in the development of DN Conclusions Our study revealed RAS genes, ACE and AGT M235T but not AGT T174M, AGTR1 or REN genotypes, as contributing factors for DN in type 2 diabetes mellitus in Chinese To clarify whether genetic variants of the renin angiotensin system (RAS) contribute to the development of diabetic nephropathy (DN) in the Chinese Methods Totally 173 Chinese subjects of Han nationality from Shanghai were classified into! Control, DN () and DN (+) groups The latter was subdivided according to the diabetic duration at the onset of DN and the stage of DN Genotyping of five polymorphic sites in four key genes of the RAS: the AGT T174M, AGT M235T and AGTR1 genotypes were determined by PCR / restriction enzyme digestion The insertion / deletion (I / D) and [ACAC] n STR microsatellite polymorphic markers were used for ACE and REN genotyping, respectively Statistical analysis showed comparisons of gene frequencies between any two groups were made with Fisher’s exact test or Chi square test Logistic regression analysis was performed to identify predictors of DN Results The frequencies of ACE DD genotype and ACE D allele were much higher in DN (+) group than in D N () group (0 25 vs 0 05, 0 47 vs 0 29, respectively), so were the frequencies of TT genotype and T allele in AGT M235T (0 73 vs 0 54, 0 85 vs 0 68, respectively) DN ( +) DUR <5 years group had large increased frequencies of AGT M235T allele and ACE DD genotype in comparison with DN () group (0 92 vs 0 68 and 0 28 vs 0 05, respectively) Logistic regression analysis further identified these two genes as contributing factors to DN Although AGTR1 and AGT T174M genotyping analysis revealed differences in frequency distribution between DN (+) and DN () or control groups, logistic regression analysis failed to implicate them in the development of DN Conclusions Our study revealed RAS genes, ACE and AGT M235T but not AGT T174M, AGTR1 or REN genotypes, as contributing factors for DN in type 2 diabetes mellitus in Chinese