Association Study Of Angiotensinase A (Enpep) Genotype With Diabetic Nephropathy

Objective: It is well known that the renin angiotensin system (RAS) plays a pivotal role in the development of diabetic nephropathy (DMN). Recent genome-wide association studies have identified a number of common genetic variants associated with blood pressure variation in east Asians. One of such loci is angiotensinase A (ENPEP), which converts the angiotensin II to angiotensin III in the RAS. We therefore tested the hypothesis that genetic variants of ENPEP could show significant association with prevalence of DMN. Design and method: We enrolled consecutive 345 subjects who had consulted our hospitals for type 2 diabetes. They consisted of cases with nephropathy (57.1 %) and controls (42.9%). Genomic DNA was isolated from human leukocytes by QIAamp kit. Genotypes were assayed with genomic DNA for a C/T variant of ENPEP (rs6825911) using the StepOnePlus real-time PCR system by TaqMan method. Association between the genetic variant and the prevalence of DMN was tested. Results: The numbers of individuals with each genotype of ENPEP were as follows (CC, CT and TT): 64, 93 and 40 for cases and 29, 84 and 35 for controls. Accordingly, the risk for DMN was 1.39 (95% confidence interval; 1.02–1.88), p = 0.03 for allelic comparison and also p = 0.03 for Armitage's trend test. Thus, a significant association with DMN was observed for the ENPEP variant with 1.4 times risk. Conclusions: Thus, it is found that a genetic variant of ENPEP may have a significant impact on the onset of DMN.