Associations between genetic variants in the ACE, AGT, AGTR1 and AGTR2 genes and renal function in the Multi-ethnic Study of Atherosclerosis.
OBJECTIVE
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.
Campbell
Catherine Y
CY
Johns Hopkins University, Baltimore, MD, USA. ccampb31@jhmi.edu
Fang
Belle F
BF
Guo
Xiuqing
X
Peralta
Carmen A
CA
Psaty
Bruce M
BM
Rich
Stephen S
SS
Young
J Hunter
JH
Coresh
Josef
J
Kramer
Holly J
HJ
Rotter
Jerome I
JI
Post
Wendy S
WS
D000368:Aged; D000808:Angiotensinogen / Q000235:genetics*; D050197:Atherosclerosis / Q000208:ethnology* / Q000235:genetics; D015331:Cohort Studies; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007674:Kidney Diseases / Q000208:ethnology* / Q000235:genetics*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics*; D012084:Renin-Angiotensin System / Q000235:genetics*
D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A