Genetic Polymorphisms and the Risk of Accelerated Renal Function Decline in Women

Background: Reduced glomerular filtration rate is an important predictor of cardiovascular disease and death. Genetic polymorphisms, particularly in genes involved in the renin-angiotensin system (RAS), may influence the rate of renal function decline. Methodology/Principal Findings: We examined the relation between specific single nucleotide polymorphisms (SNPs), including those in the RAS, apolipoprotein E and alpha-adducin, and renal function decline assessed by estimated glomerular filtration rate (eGFR) over an 11-year period in 2578 Caucasian participants of the Nurses ’ Health Study. Logistic regression was used to examine the associations between genotype and risk of eGFR decline of $25%. Results: After 11 years between creatinine measurements, the eGFR declined by $25 % in 423 of 2578 (16%) women. The angiotensinogen (AGT) A-20C polymorphism was associated with a higher risk of renal function decline when two risk alleles were present than if one or no alleles were present (CC vs AA and AC) OR 1.83 (95 % CI 1.02–3.26; p = 0.04). The angiotensin II type 1 receptor (AT1R) A1166C polymorphism was marginally associated with a higher risk of renal function decline when two risk alleles were present (CC vs AA, OR = 1.41; 95 % CI 0.98–2.01; p = 0.06). The alpha-adducin G460