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Association of polymorphisms in NOS3 with the ankle-brachial index in hypertensive adults.

ABSTRACT: We investigated the association of 14 polymorphisms in the endothelial nitric oxide synthase gene (NOS3) with ankle brachial index (ABI) in non-Hispanic white hypertensives belonging to hypertensive sibships. Subjects (n=659, mean age 61+/-9 years, 54% women) underwent measurement of ABI using a standard protocol, and the lowest of 4 ABI values was used in the analyses. Non-synonymous SNPs with a minor allele frequency >0.02 and tag SNPs selected based on a measure of linkage disequilibrium (r(2)) were genotyped. We reduced the chance of false positives by testing for replication, randomly selecting 1 hypertensive sib from each sibship to create Subset 1 (n=330) and Subset 2 (n=329). Multivariable linear regression models were used to assess the associations of single NOS3 polymorphisms and haplotypes with ABI after adjustment for covariates (age, sex, body mass index, smoking, total cholesterol, HDL cholesterol, and diabetes). Two specific SNPs in significant LD with each other (rs891512 and rs1808593) were significantly associated with ABI in both subsets. Based on a sliding window approach with a window size of 2, estimated haplotypes from 2 SNP pairs (rs2070744-rs3918226 and rs1808593-rs7830) were also significantly associated with ABI in both subsets. In conclusion, specific NOS3 SNPs and haplotypes were associated with inter-individual variation in ABI, a non-invasive marker of peripheral arterial disease, in replicate subsets of hypertensive subjects. These findings motivate further investigation of the role of NOS3 variants in determining susceptibility to peripheral arterial disease.

SUBMITTER: Kullo IJ

PROVIDER: S-EPMC2858046 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature

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Association of polymorphisms in NOS3 with the ankle-brachial index in hypertensive adults.

Kullo Iftikhar J IJ Greene M Todd MT Boerwinkle Eric E Chu Jian J Turner Stephen T ST Kardia Sharon L R SL

Atherosclerosis 20070323 2

We investigated the association of 14 polymorphisms in the endothelial nitric oxide synthase gene (NOS3) with ankle brachial index (ABI) in non-Hispanic white hypertensives belonging to hypertensive sibships. Subjects (n=659, mean age 61+/-9 years, 54% women) underwent measurement of ABI using a standard protocol, and the lowest of 4 ABI values was used in the analyses. Non-synonymous SNPs with a minor allele frequency >0.02 and tag SNPs selected based on a measure of linkage disequilibrium (r(2 ...[more]

PMID: 17367796

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Project description:BackgroundErectile dysfunction (ED) is a very common condition among adult men and its prevalence increases with age. The ankle-brachial blood pressure index (ABPI) is a noninvasive tool used to assess peripheral vascular disease (PAD) and vascular stiffness. However, the association between ABPI and ED is unclear. We aimed to explore the association between ABPI and ED in the US population.MethodsOur study used data from two separate National Health and Nutrition Examination Survey (NHANES) datasets (2001-2002 and 2003-2004). Survey-weighted logistic regression models were used to explore the association between ABPI as a continuous variable and quartiles with ED. We further assessed the association between ABPI and ED using restricted cubic regression while selecting ABPI thresholds using two-piecewise Cox regression models. In addition, we performed subgroup analyses stratified by BMI, race, marital status, diabetes, and hypertension.Main outcome measureABPI was calculated by dividing the mean systolic blood pressure at the ankle by the mean systolic blood pressure at the arm.ResultsFinally, 2089 participants were enrolled in this study, including 750 (35.90%) ED patients and 1339 (64.10%) participants without ED. After adjusting for all confounding covariates, logistic regression analyses showed a significant association between ABPI and ED (OR=0.19; 95% CI, 0.06-0.56, P=0.01); with ABPI as a categorical variable, compared with the lowest quartile, the OR and 95% CI for the second quartile were 0.58 (0.34-0.97; P = 0.04).Besides, splines indicated that there was an L-shaped relationship between ABPI levels and the risk of ED. Piecewise Cox regression demonstrated the inflection point at 1.14, below which the OR for ED was 0.06 (0.02-0.20; P < 0.001), and above which the OR was 2.79 (0.17-4.53; P = 0.469).ConclusionIn our study, lower ABPI was independently associated with ED risk. In addition, the lowest ABPI level associated with ED risk was 1.14, below this level, lower ABPI was associated with higher ED risk.

Dataset Information

Association of polymorphisms in NOS3 with the ankle-brachial index in hypertensive adults.

Publications

Association of polymorphisms in NOS3 with the ankle-brachial index in hypertensive adults.

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