Published Online
on August 11, 2005

A more recent version of this article appeared on September 1, 2005

This Article Full Text (PDF) All Versions of this Article: 36/9/1848    most recent 01.STR.0000177978.97428.53v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Howard, T. D. Articles by Kittner, S. J. Search for Related Content PubMed PubMed Citation Articles by Howard, T. D. Articles by Kittner, S. J. Related Collections Epidemiology Genomics Genetics of Stroke Related Articles

Submitted on February 20, 2005
Revised on April 13, 2005
Accepted on May 3, 2005

Promoter Polymorphisms in the Nitric Oxide Synthase 3 Gene Are Associated With Ischemic Stroke Susceptibility in Young Black Women

Timothy D. Howard PhD; Wayne H. Giles MD, MPH; Jianfeng Xu MD, DrPH; Marcella A. Wozniak MD, PhD; Ann M. Malarcher PhD, MSPH; Leslie A. Lange PhD; Richard F. Macko MD; Monica J. Basehore; Deborah A. Meyers PhD; John W. Cole MD; and Steven J. Kittner MD, MPH^*

From the Center for Human Genomics (T.D.H., J.X., M.J.B., D.A.M.), Wake Forest University School of Medicine, Winston-Salem, NC; Division of Adult and Community Health (W.H.G., A.M.M.), Centers for Disease Control and Prevention, Atlanta, Ga; Department of Neurology (M.A.W., R.F.M., J.W.C., S.J.K.) and the Department of Epidemiology and Preventive Medicine (S.J.K.), University of Maryland at Baltimore, Md; the Geriatrics Research, Education, and Clinical Center (R.F.M., J.W.C., S.J.K.), Baltimore Department of Veterans Affairs Medical Center, Md; and Department of Genetics (L.A.L.), University of North Carolina, Chapel Hill.

^* To whom correspondence should be addressed. E-mail: skittner{at}umaryland.edu.

Background and Purpose--Endothelial nitric oxide exerts a variety of protective effects on endothelial cells and blood vessels, and therefore the nitric oxide synthase 3 gene (NOS3) is a logical candidate gene for stroke susceptibility.

Methods--We used the population-based Stroke Prevention in Young Women case-control study to assess the association of five NOS3 polymorphisms in 110 cases (46% black) with ischemic stroke and 206 controls (38% black), 15 to 44 years of age. Polymorphisms included 3 single nucleotide polymorphisms (SNPs) in the promoter region (-1468 T>A, -922 G>A, -786 T>C), 1 SNP in exon 7 (G894T), and 1 insertion/deletion polymorphism within intron 4.

Results--Significant associations with both the -922 G>A and -786 T>C SNPs with ischemic stroke were observed in the black, but not the white, population. This association was attributable to an increased prevalence of the -922 A allele (OR=3.0, 95% CI=1.3 to 6.8; P=0.005) and the -786 T allele (OR=2.9, 95% CI=1.3 to 6.4; P=0.005) in cases versus controls. These 2 SNPs were in strong linkage disequilibrium (D'=1.0), making it impossible to determine, within the confines of this genetic study, whether 1 or both of these polymorphisms are functionally related to NOS3 expression. Two sets of haplotypes were also identified, 1 of which may confer an increased susceptibility to stroke in blacks, whereas the other appears to be protective.

Conclusion--Promoter variants in NOS3 may be associated with ischemic stroke susceptibility among young black women.

Key words: genetics • nitric oxide • women and minorities • young, stroke in

Related Articles:

Editorial Comment—Are We in Another Unavoidable ‘Diagnose and Adios’ Era?

Tsong-Hai Lee and Ku-Chou Chang
Stroke 2005 36: 1852-1853. [Full Text] [PDF]

Are We in Another Unavoidable ‘Diagnose and Adios’ Era?

Tsong-Hai Lee and Ku-Chou Chang
Stroke 2005 0: 01.STR.0000177875.02241.41v1. [Abstract] [PDF]

This article has been cited by other articles:

				N. U. Ko, P. Rajendran, H. Kim, M. Rutkowski, L. Pawlikowska, P.-Y. Kwok, R. T. Higashida, M. T. Lawton, W. S. Smith, J. G. Zaroff, et al. Endothelial Nitric Oxide Synthase Polymorphism (-786T->C) and Increased Risk of Angiographic Vasospasm After Aneurysmal Subarachnoid Hemorrhage Stroke, April 1, 2008; 39(4): 1103 - 1108. [Abstract] [Full Text] [PDF]

				J. P. Casas, G. L. Cavalleri, L. E. Bautista, L. Smeeth, S. E. Humphries, and A. D. Hingorani Endothelial Nitric Oxide Synthase Gene Polymorphisms and Cardiovascular Disease: A HuGE Review Am. J. Epidemiol., November 15, 2006; 164(10): 921 - 935. [Abstract] [Full Text] [PDF]

				C. D. Bushnell, P. Hurn, C. Colton, V. M. Miller, G. del Zoppo, M. S.V. Elkind, B. Stern, D. Herrington, G. Ford-Lynch, P. Gorelick, et al. Advancing the Study of Stroke in Women: Summary and Recommendations for Future Research From an NINDS-Sponsored Multidisciplinary Working Group Stroke, September 1, 2006; 37(9): 2387 - 2399. [Abstract] [Full Text] [PDF]

				O. Appenzeller, V. E. Claydon, G. Gulli, C. Qualls, M. Slessarev, G. Zenebe, A. Gebremedhin, and R. Hainsworth Cerebral Vasodilatation to Exogenous NO Is a Measure of Fitness for Life at Altitude * Online Material Stroke, July 1, 2006; 37(7): 1754 - 1758. [Abstract] [Full Text] [PDF]

				T.-H. Lee and K.-C. Chang Editorial Comment--Are We in Another Unavoidable 'Diagnose and Adios' Era? Stroke, September 1, 2005; 36(9): 1852 - 1853. [Full Text] [PDF]