| Objective: To investigate whether three polymorphisms in the renin-angiotensin system(RAS)―ACE I/D,AGT M235T and AGT T174M―are associated with type 2 diabetes mellitus(DM) and diabetic nephropathy(DN) in Guangxi people. Methods: A case-control study was performed. Totally 243 subjects from Guangxi were classified into DM group(n=107) and control group(n=136). The former was divided into DN(+) group(n=53) and DN(-) group(n=54) according to with or without DN.The ACE I/D, AGT M235T and AGT T174M polymorphisms were examed by polymerase chain reaction(PCR), mutagenically separated PCR(MS-PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP),respectively.Results:(1)The frequencies of ACE-DD genotype and ACE D allele were significantly higher in DM group than in control group (0.168 vs 0.081,P=0.0007； 0.453 vs 0.294,P=0.0003, respectively).(2) The ACE I/D polymorphism did not show any difference in allelic frequency and genotype distribution between DN(+) and DN(-) groups.(3) The genotype found in AGT M235T polymorphic site was mostly TT type in three groups (0.717,0.667 and 0.640, respectively).No significant differences in AGT M235T genotypes and allelic frequencies among three groups. (4) The AGT T174M polymorphism did not display any difference in allelic frequencies and genotype distribution among DN(+),DN(-) and controls. (5) DN(+) OR associated with a combined genotype(ACE-DD+AGT M235T-TT) was 3.85,DN(-) OR associated with this combined genotype was 3.23.Both were increased than those associated with single ACE-DD or AGT M235T-TT genotype. Conclusions: (1) ACE I/D polymorphism is associated with type 2 diabetes mellitus in Guangxi population,ACE-DD genotype and D allele may be the risk factors in type 2 DM. (2) None of three polymorphisms we studied(ACE I/D,AGT M235T,AGT T174M ) contributes to genetic susceptibility to DN in type 2 diabetic patients. (3) Our findings suggest a synergistic effect between ACE-DD genotype and AGT M235T-TT genotype on DN in type 2 diabetes mellitus.
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