Endothelial Nitric Oxide Synthase Gene Polymorphisms and Cardiovascular Disease: A HuGE Review (original) (raw)

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Correspondence to Dr. Aroon D. Hingorani, Centre for Clinical Pharmacology, BHF Laboratories at UCL, Rayne Building, 5 University Street, London WC1E 6JJ, United Kingdom (e-mail: a.hingorani@ucl.ac.uk).

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Published:

03 October 2006

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Juan P. Casas, Gianpiero L. Cavalleri, Leonelo E. Bautista, Liam Smeeth, Steve E. Humphries, Aroon D. Hingorani, Endothelial Nitric Oxide Synthase Gene Polymorphisms and Cardiovascular Disease: A HuGE Review, American Journal of Epidemiology, Volume 164, Issue 10, 15 November 2006, Pages 921–935, https://doi.org/10.1093/aje/kwj302
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Abstract

This review examines the association of a subset of endothelial nitric oxide synthase gene (NOS3) polymorphisms (Glu298Asp, intron 4, and -786T>C) with cardiovascular disease. The Glu298Asp polymorphism within exon 7 is the only common nonsynonymous variant. The variants have been associated with low plasma nitric oxide concentrations and reduced vascular reactivity; difficulties in measuring those phenotypes means that their functional role remains unclear. A large meta-analysis of NOS3 polymorphisms in coronary heart disease revealed per-allele odds ratios of 1.17 (95% confidence interval: 1.07, 1.28) for Glu298Asp, 1.17 (95% confidence interval: 1.07, 1.28) for -786T>C, and 1.12 (95% confidence interval: 1.01, 1.24) for intron 4. However, there was evidence that small studies with more striking results could affect the associations of the Glu298Asp and -786T>C polymorphisms with coronary heart disease. Associations of NOS3 polymorphisms with hypertension, preeclampsia, stroke, and diabetes remain uncertain. To date, no reliable gene-gene or gene-environmental interactions have been described. Use of these variants in predictive testing is unlikely to be useful, although the population attributable fraction could be substantial if the modest associations are causal. The need for large-scale genetic association studies using tagging polymorphisms is warranted to confirm or refute a role of the NOS3 gene in coronary heart disease.

CHD, coronary heart disease, CI, confidence interval, eNOS, endothelial nitric oxide synthase, OR, odds ratio, SNP, single nucleotide polymorphism, tSNP, tagging single nucleotide polymorphism

American Journal of Epidemiology Copyright © 2006 by the Johns Hopkins Bloomberg School of Public Health All rights reserved; printed in U.S.A.

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