Dataset Information

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

ABSTRACT: 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.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.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.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.

SUBMITTER: Campbell CY

PROVIDER: S-EPMC2941827 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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

Campbell Catherine Y CY 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

American journal of nephrology 20100701 2

<h4>Background/aims</h4>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.<h4>Methods</h4>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 di ...[more]

PMID: 20606419

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Project description:Renal artery calcium (RAC) has been shown to be associated with higher odds of hypertension (HTN). The purpose of this study was to determine if the presence and extent of RAC is associated with renal function. We analyzed cross-sectional data from the Multi-Ethnic Study of Atherosclerosis (MESA). A subsample of 1,226 participants underwent computed tomography of the abdomen and also had venous blood samples measured for kidney function. RAC was the primary predictor variable and the following measures of kidney function were the outcome variables: estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), and chronic kidney disease (CKD) stage. The analyses were adjusted for age, gender, race, height, visceral fat, dyslipidemia, diabetes, cigarette smoking, hypertension, interleukin-6 and abdominal aortic calcium (AAC). The average age of this cohort was 66.1 years (SD 9.7), 44.8% (549 of 1,226) were men, and nearly 30% had RAC?>0. Compared with those with no RAC, those with RAC?>0 were significantly older but not different by gender or race. After adjustment for age, gender, and race, those with RAC?>0 had significantly higher visceral fat, were more likely to have dyslipidemia, diabetes, and hypertension, had a higher interleukin-6, and a higher prevalence of AAC?>0. The mean eGFR and UACR among those without RAC were 80?ml/min/1.73?m2 and 21?mg/g, whereas these values were 78?ml/min/1.73?m2 and 55?mg/g among those with RAC. In fully adjusted multivariable linear regression models, the presence of RAC was associated with a lower eGFR (??=?-2.21, p?=?0.06) but not with UACR (??=?0.02, p?=?0.79). In fully adjusted ordinal logistic regression, RAC as a continuous variable was associated with increased odds of being in a worse CKD category (odds ratio?1.14, p?=?0.05). When measured by eGFR and CKD stage, there is a modest relation between RAC and kidney function. Further studies might involve clinical trials to assess the role of intensive cardiovascular disease risk factor management in patients with subclinical RAC to determine if this may prevent or delay the development and progression of CKD.

Dataset Information

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

Publications

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

Similar Datasets

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