Associations between genetic variants in the ace, agt, agtr1 and agtr2 genes and renal function in the multi-ethnic study of atherosclerosis

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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)156-162
Number of pages7
JournalAmerican Journal of Nephrology
Volume32
Issue number2
DOIs
StatePublished - Jan 1 2010

Keywords

  • Ace
  • Agt
  • Agtr1
  • Agtr2
  • Albuminuria
  • Creatinine clearance epidemiology
  • Genetics
  • Renin-Angiotensin

ASJC Scopus subject areas

  • Nephrology

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