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(Hypertension. 2004;44:668.)
© 2004 American Heart Association, Inc.

Scientific Contributions

Gender-Specific Influence of NO Synthase Gene on Blood Pressure Since Childhood

The Bogalusa Heart Study

Wei Chen; Sathanur R. Srinivasan; Shengxu Li; Eric Boerwinkle; Gerald S. Berenson

From the Tulane Center for Cardiovascular Health and Department of Epidemiology (W.C., S.R.S., S.L., G.S.B.), Tulane University Health Sciences Center, New Orleans, La; and Human Genetics Center and Institute of Molecular Medicine (E.B.), University of Texas-Houston Health Science Center.

Reprint requests to Gerald S. Berenson, MD, Tulane Center for Cardiovascular Health, 1440 Canal St, Suite 1829, New Orleans, LA 70112. E-mail berenson{at}tulane.edu

Impaired endothelial function caused by decreased NO production plays a pathophysiologic role in essential hypertension. Although cross-sectional data are available on the association between endothelial NO synthase gene polymorphisms and hypertension, whether the gene variants and their haplotypes affect the long-term cumulative burden and trend of blood pressure since childhood is not known. This aspect was examined using 4 polymorphisms and a community-based longitudinal cohort of 347 blacks and 801 whites aged 18 to 45 years who have been examined serially 4 to 13 times (7705 observations) over an on average of 23.4 years. The area under the curve calculated using a growth curve of serial measurements of mean arterial pressure was used as a long-term cumulative burden. Blacks compared with whites displayed significantly lower frequencies of the rare alleles for G894T (0.112 versus 0.325), G10T (0.209 versus 0.323), T-786C (0.147 versus 0.372), and A-922G (0.131 versus 0.355). In addition, T-786C and A-922G polymorphisms were in complete linkage disequilibrium in both races. After adjusting for age and body mass index, the 894T and 10T alleles were significantly associated with lower long-term burden of blood pressure since childhood in black females and white females, respectively. With respect to haplotypes, the G894-10T carriers compared with (G894-G10)/(G894-G10) showed significantly lower long-term burden and trend of blood pressure in white females. In conclusion, the endothelial NO synthase gene influences the long-term burden and trend of blood pressure since childhood in females and may contribute to their predisposition to hypertension.

Key Words: nitric oxide synthase • haplotypes • blood pressure

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