The role of renin–angiotensin–aldosterone system genes in the progression of chronic kidney disease: findings from the Chronic Renal Insufficiency Cohort (CRIC) study

摘要: BACKGROUND We conducted single-marker, gene- and pathway-based analyses to examine the association between renin-angiotensin-aldosterone system (RAAS) variants chronic kidney disease (CKD) progression among Chronic Renal Insufficiency Cohort study participants. METHODS A total of 1523 white 1490 black subjects were genotyped for 490 single nucleotide polymorphisms (SNPs) in 12 RAAS genes as part ITMAT-Broad-CARe array. CKD phenotypes included decline estimated glomerular filtration rate (eGFR) over time occurrence a renal event, defined incident end-stage or halving eGFR from baseline. Mixed-effects models used SNP associations with decline, while Cox proportional hazards tested events. Gene- using truncated product method. All stratified by race, Bonferroni correction was applied adjust multiple testing. RESULTS Among participants, declined an average 1.2 2.3 mL/min/1.73 m(2)/year, respectively, events occurred respective 11.5 24.9% identified strong progression. The AGT RENBP consistently associated risk separate participants (both P < 1.00 × 10(-6)). Driven significant gene-based findings, entire pathway also both groups No single-marker observed. CONCLUSIONS current provides evidence role