Associations between genetic variants in the ACE, AGT, AGTR1 and AGTR2 genes and renal function in the Multi-ethnic Study of Atherosclerosis

Am J Nephrol. 2010;32(2):156-62. doi: 10.1159/000315866. Epub 2010 Jul 1.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Angiotensinogen / genetics*
  • Atherosclerosis / ethnology*
  • Atherosclerosis / genetics
  • Cohort Studies
  • Ethnicity / genetics*
  • Female
  • Genetic Variation
  • Humans
  • Kidney Diseases / ethnology*
  • Kidney Diseases / genetics*
  • Kidney Function Tests
  • Male
  • Middle Aged
  • Peptidyl-Dipeptidase A / genetics*
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Receptor, Angiotensin, Type 1 / genetics*
  • Receptor, Angiotensin, Type 2 / genetics*
  • Renin-Angiotensin System / genetics*

Substances

  • Receptor, Angiotensin, Type 1
  • Receptor, Angiotensin, Type 2
  • Angiotensinogen
  • Peptidyl-Dipeptidase A