Journal Article

Endothelial Nitric Oxide Synthase (<i>NOS3</i>) Genetic Variants, Maternal Smoking, Vitamin Use, and Risk of Human Orofacial Clefts

Gary M. Shaw, David M. Iovannisci, Wei Yang, Richard H. Finnell, Suzan L. Carmichael, Suzanne Cheng and Edward J. Lammer

in American Journal of Epidemiology

Published on behalf of Johns Hopkins Bloomberg School of Public Health

Volume 162, issue 12, pages 1207-1214
Published in print December 2005 | ISSN: 0002-9262
Published online November 2005 | e-ISSN: 1476-6256 | DOI:
Endothelial Nitric Oxide Synthase (NOS3) Genetic Variants, Maternal Smoking, Vitamin Use, and Risk of Human Orofacial Clefts

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Orofacial clefts have been associated with maternal cigarette smoking and lack of folic acid supplementation (which results in higher plasma homocysteine concentrations). Because endothelial nitric oxide synthase (NOS3) activity influences homocysteine concentration and because smoking compromises NOS3 activity, genetic variation in NOS3 might interact with smoking and folic acid use in clefting risk. The authors genotyped 244 infants with isolated cleft lip with or without cleft palate (CL/P), 99 with isolated cleft palate, and 588 controls from a California population-based case-control study (1987–1989 birth cohort) for two NOS3 polymorphisms: A(−922)G and G894T. Analyses of gene-only effects for each polymorphism revealed a 60% increased risk of CL/P among NOS3 A(−922)G homozygotes (odds ratio (OR) = 1.6, 95% confidence interval (CI): 1.0, 2.6). There was some evidence for higher risk of CL/P with maternal periconceptional smoking in infants with an NOS3 −922G allele (for homozygotes, OR = 2.5, 95% CI: 1.2, 5.6) but not in those with an 894T allele. For CL/P risk, odds ratios were over 4 among mothers who smoked, who did not use vitamins, and whose infants had at least one variant allele for each NOS3 polymorphism (for A(−922)G, OR = 4.6, 95% CI: 2.1, 10.2; for 894T, OR = 4.4, 95% CI: 1.8, 10.7). No similar patterns were observed for risk of cleft palate.

Keywords: abnormalities; cleft lip; cleft palate; genetics; nitric-oxide synthase; risk factors; smoking; vitamins; NCBI, National Center for Biotechnology Information; NOS3, endothelial nitric oxide synthase; SNP, single nucleotide polymorphism

Journal Article.  4649 words. 

Subjects: Public Health and Epidemiology

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