Associations between Genetic Variants in the ACE, AGT, AGTR1 and AGTR2 Genes and Renal Function in the Multi-Ethnic Study of Atherosclerosis

作者：Campbell Catherine Y^*; Fang Belle F; Guo Xiuqing; Peralta Carmen A; Psaty Bruce M; Rich Stephen S; Young J Hunter; Coresh Josef; Kramer Holly J; Rotter Jerome I; Post Wendy S

来源：American Journal of Nephrology, 2010, 32(2): 156-162.

DOI：10.1159/000315866

• Renin-angiotensin
• ACE
• AGT
• AGTR1
• AGTR2
• Albuminuria
• Creatinine clearance epidemiology
• Genetics

Background/Aims: Some studies suggest that polymorphisms in angiotensin-converting enzyme (ACE), angiotensinogen (AGT), angiotensin II type I receptor (AGTR1) and angiotensin II type II receptor (AGTR2) genes may contribute to renal function variation. Methods: Genotyping for single nucleotide polymorphisms (SNPs) in these candidate genes was performed in 2,847 participants from four racial/ethnic groups (African American, Chinese, White and Hispanic) without known cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis. SNP and haplotype analyses were performed to determine associations between genotypes and cross-sectional renal function measurements, including urine albumin excretion (UAE) and estimated glomerular filtration rate (eGFR) using serum creatinine and cystatin C. Results: Twenty-four ACE SNPs, 10 AGT SNPs, 15 AGTR1 SNPs and 6 AGTR2 SNPs were typed successfully. After adjusting for ancestry, age and gender, 3 SNPs (AGT M235T, AGT rs2148582 and AGTR1 rs2131127) showed associations with an empiric p value <0.05 with the same phenotype in multiple racial/ethnic groups, suggesting replication. The AGT M235T SNP has been shown previously to be associated with diabetic and hypertensive nephropathy. Conclusions: These data suggest that genetic polymorphisms in the renin-angiotensin system are associated with renal phenotypes in the general population, but that many associations differ across racial/ethnic groups.

• 出版日期2010