The A1166C polymorphism of angiotensin II Type 1 receptor as a predictor of renal function decline over 4 years follow-up in an apparently healthy Chinese population

Abstract

The angiotensin II Type 1 receptor (AT1R) A1166C (rs5186) genez polymorphism is equivocally associated with the patients' susceptibility to chronic kidney disease or end-stage renal disease. We conducted a prospective study to investigate the influence of AT1R A1166C gene polymorphism on the quantitative changes of renal function. Of 1500 people screened, 112 non-diabetic normotensive elderly Chinese were recruited and received biochemistry examination at the baseline, at the second and fourth year follow-up. Serum creatinine and calculated renal parameters, using Cockroft-Gault (CG) formula, Modification of Diet in Renal Disease (MDRD) Study and abbreviated MDRD (abMDRD) equation, were used to evaluate renal function and their progression. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism. Age was 71.9 +/- 3.7 years (range 60 - 81). Serum creatinine, CG creatinine clearance (CrCl), MDRD and abMDRD glomerular filtration rate (GFR) were significantly decreased at the 2 and 4-year follow-up (all p < 0.001). The magnitude of 4-year decline of above four renal parameters was significantly higher in subjects carrying the AT1R AA genotype than C-allele carriers (p = 0.014, 0.033, 0.008 and 0.014 for creatinine, CG CrCl, MDRD and abMDRD GFR, respectively). This association was still significant in multivariate analyses (p = 0.019, 0.045, 0.035 and 0.018, respectively). This longitudinal study showed that the aging process was associated with decline of renal function in the healthy elderly. The AT1R A1166C gene polymorphism might modulate these changes in the Chinese. This provides further knowledge essential in the assessment of renal disease and determination of renal function in the older subjects.