American Journal of Epidemiology Advance Access originally published online on October 3, 2006
American Journal of Epidemiology 2006 164(10):921-935; doi:10.1093/aje/kwj302
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Human Genome Epidemiology (HuGE) Review |
Endothelial Nitric Oxide Synthase Gene Polymorphisms and Cardiovascular Disease: A HuGE Review
1 Centre for Clinical Pharmacology, Department of Medicine, British Heart Foundation Laboratories at University College London, London, United Kingdom
2 Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom
3 The Institute for Genome Science and Policy, Duke University, Durham, NC
4 Population Health Sciences, University of Wisconsin Medical School, Madison, WI
5 Centre for Cardiovascular Genetics, Department of Medicine, British Heart Foundation Laboratories at University College London, London, United Kingdom
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{at}ucl.ac.uk).
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.
cardiovascular diseases; epidemiology; genotype; meta-analysis; nitric oxide synthase type III; NOS3; polymorphism, genetic; pre-eclampsia
Abbreviations: CHD, coronary heart disease; CI, confidence interval; eNOS, endothelial nitric oxide synthase; OR, odds ratio; SNP, single nucleotide polymorphism; tSNP, tagging single nucleotide polymorphism
Editor's note: This paper is also available on the website of the Human Genome Epidemiology Network (http://www.cdc.gov/genomics/hugenet/).
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. H. Kang, J. L. Wiggs, B. A. Rosner, S. E. Hankinson, W. Abdrabou, B. J. Fan, J. Haines, and L. R. Pasquale Endothelial Nitric Oxide Synthase Gene Variants and Primary Open-Angle Glaucoma: Interactions with Sex and Postmenopausal Hormone Use Invest. Ophthalmol. Vis. Sci., February 1, 2010; 51(2): 971 - 979. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Oosterveer, J. Versmissen, M. Yazdanpanah, J. C. Defesche, J. J.P. Kastelein, and E. J.G. Sijbrands The risk of tendon xanthomas in familial hypercholesterolaemia is influenced by variation in genes of the reverse cholesterol transport pathway and the low-density lipoprotein oxidation pathway Eur. Heart J., December 16, 2009; (2009) ehp538v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Gluba, M. Banach, J. Rysz, G. Piotrowski, W. Fendler, and T. Pietrucha Is Polymorphism Within eNOS Gene Associated With the Late Onset of Myocardial Infarction? A Pilot Study Angiology, October 1, 2009; 60(5): 588 - 595. [Abstract] [PDF]
|
|
|
|
 |
|
 H. Kim, S. Y. Ku, S. H. Kim, G. H. Lee, Y. M. Choi, J. M. Kim, T. H. Lee, and S. Y. Moon Endothelial nitric oxide synthase gene Glu298Asp polymorphism is associated with advanced stage endometriosis Hum. Reprod., October 1, 2009; 24(10): 2656 - 2659. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Schwedt Endothelial Dysfunction in Migrainece Cephalalgia, September 1, 2009; 29(9): 997 - 1002. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Madhere, J. Harrell, and C. D. M. Royal Social Ecology, Genomics, and African American Health: A Nonlinear Dynamical Perspective. Journal of Black Psychology, January 1, 2009; 35(2): 154 - 179. [Abstract] [PDF]
|
|
|
|
 |
|
 A. Thompson, E. Di Angelantonio, N. Sarwar, S. Erqou, D. Saleheen, R. P. F. Dullaart, B. Keavney, Z. Ye, and J. Danesh Association of Cholesteryl Ester Transfer Protein Genotypes With CETP Mass and Activity, Lipid Levels, and Coronary Risk JAMA, June 18, 2008; 299(23): 2777 - 2788. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Thameem, S. Puppala, N. H Arar, M. P Stern, J. Blangero, R. Duggirala, and H. E Abboud Endothelial nitric oxide synthase (eNOS) gene polymorphisms and their association with type 2 diabetes-related traits in Mexican Americans Diabetes and Vascular Disease Research, June 1, 2008; 5(2): 109 - 113. [Abstract] [PDF]
|
|
|
|
 |
|
 E. Zintzaras, G. Raman, G. Kitsios, and J. Lau Angiotensin-Converting Enzyme Insertion/Deletion Gene Polymorphic Variant as a Marker of Coronary Artery Disease: A Meta-analysis Arch Intern Med, May 26, 2008; 168(10): 1077 - 1089. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Galluccio, P. Piatti, L. Citterio, P. C. G. Lucotti, E. Setola, L. Cassina, M. Oldani, I. Zavaroni, E. Bosi, A. Colombo, et al. Hyperinsulinemia and impaired leptin-adiponectin ratio associate with endothelial nitric oxide synthase polymorphisms in subjects with in-stent restenosis Am J Physiol Endocrinol Metab, May 1, 2008; 294(5): E978 - E986. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Prisant Nebivolol: Pharmacologic Profile of an Ultraselective, Vasodilatory {beta}1-Blocker J. Clin. Pharmacol., February 1, 2008; 48(2): 225 - 239. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Mata-Greenwood and D.-B. Chen Racial Differences in Nitric Oxide--Dependent Vasorelaxation Reproductive Sciences, January 1, 2008; 15(1): 9 - 25. [Abstract] [PDF]
|
|
|
|
|
|
A. M. Bennet, E. Di Angelantonio, Z. Ye, F. Wensley, A. Dahlin, A. Ahlbom, B. Keavney, R. Collins, B. Wiman, U. de Faire, et al. Association of Apolipoprotein E Genotypes With Lipid Levels and Coronary Risk JAMA, September 19, 2007; 298(11): 1300 - 1311. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. T. Cirulli and D. B. Goldstein In vitro assays fail to predict in vivo effects of regulatory polymorphisms Hum. Mol. Genet., August 15, 2007; 16(16): 1931 - 1939. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. P. Rossi and M. Cesari Reply J. Am. Coll. Cardiol., March 20, 2007; 49(11): 1226 - 1227. [Full Text] [PDF]
|
|