Genetic polymorphisms of the renin-angiotensin-aldosterone system in Chinese patients with end-stage renal disease secondary to IgA nephropathy

Background Genetic variability in the renin-angiotensin-aldosterone system may modify renal responses to injury and disease progression The angiotensin l-converting enzyme (ACE) gene insertion/deletion (VD), the angiotensinogen (AGT) gene, M235T, the aldosterone synthase (CYP11B2) gene, C-344T, and the angiotensin II type 1 receptor (AT1R) gene, A1166C, have been shown to be associated with IgA nephropathy (IgAN) and its progression We determined the presence of these polymorphisms in 130 Chinese patients with IgAN, including 47 patients with end-stage renal disease (ESRD) and 120 healthy Chinese subjects, to assess their impact on the susceptibility to disease and the liability of progression to ESRD Methods Genotyping was performed with DNA isolated from peripheral leucocytes using polymerase chain reaction amplification of the polymorphic sequence, restriction enzyme digestion, and separation and identification of DNA fragments Clinical data from renal biopsies were collected Results ACE, AGT, CYP and AT1R genotype distributions were similar in patients with IgAN and in controls Comparing patients with ESRD (IgAN-ESRD) and those without ESRD (IgAN-non ESRD), there was a significant increase only in the ACE DD genotype (P < 0 05) among the four gene polymorphisms There was significant dominance of the male (P < 005), more marked hypertension (P < 001), proteinuria (P < 001) and increased serum creatinine during renal biopsy (P < 0 01) in the IgAN-ESRD group Conclusion Among the ACE, AGT, AT1R and CYP gene polymorphisms, only the DD genotype may predispose the individual to increased risk of progression to ESRD in the Chinese population Chin Med J 2010,123(22) 3238-3242