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Endothelial nitric oxide synthase polymorphism, nitric oxide production, salt sensitivity and cardiovascular risk factors in Hispanics

Journal of Human Hypertension volume 19, pages 233–240 (2005)Cite this article

Abstract

Mutations in the endothelial nitric oxide synthase (eNOS) gene may be associated with abnormal nitric oxide (NO) production and cardiovascular diseases. In this study, we investigated the prevalence of two eNOS polymorphisms, the Glu298Asp variant on exon 7, and the 4a/b variable number of tandem repeats (VNTR) on intron 4, and their association with blood pressure (BP), NO production, salt sensitivity and cardiovascular risk factors in healthy Venezuelans. The prevalence of both polymorphisms in Venezuelans was comparable to that described for Caucasians, but significantly different from that known for African-Americans and Japanese. The 4a/b genotype was associated with reduced levels of NO metabolites (25% decrease), larger BP lowering in response to salt restriction (9.0 vs 4.8 mmHg, P<0.05), greater prevalence of salt sensitivity (39% in 4a/b and 27% in 4b/b; P<0.05) and with higher LDL-cholesterol levels. The Glu298T polymorphism did not affect NO production, nor it was associated with salt sensitivity. Glu298Asp polymorphism was positively associated with higher weight, triglycerides and LDL-cholesterol. Neither polymorphism was associated with changes in fasting or postload serum glucose, BP, obesity and albuminuria. In conclusion, the prevalence of eNOS polymorphisms is strongly determined by ethnic factors. The 4a/b gene polymorphism could be a genetic susceptibility factor for the BP response to salt intake and for the genetic control of NO production. The reduced NO production in subjects with the 4a/b genotype may be responsible for the increased sensitivity of their BP to salt.

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Acknowledgements

This study was supported by FONACIT S1-2001000679, CDCH-06.30.4362.03, CDCH-06-10.4214.01, Scientific Initiative of the Millennium No. BIRF-VE. Sub-project ‘Center for the Detection and Treatment of Silent Risk Factors for Cardiovascular and Metabolic Diseases' to ISH and LCX, and NSU President's Faculty Scholarship Award to LCX, 2002.

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Authors and Affiliations

  1. Center for the Detection and Treatment of Silent Risk Factors for Cardiovascular and Metabolic Disease, Division of Clinical Pharmacology Unit, School of Pharmacy, Central University of Venezuela,

    I S Hoffmann, A B Alfieri & L X Cubeddu

  2. Department of Pharmaceutical Sciences, College of Pharmacy, Health Professions Division, NOVA Southeastern University (NSU), Fort Lauderdale, FL, USA

    R Tavares-Mordwinkin, A M Castejon & L X Cubeddu

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  1. I S Hoffmann
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  2. R Tavares-Mordwinkin
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  3. A M Castejon
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  4. A B Alfieri
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  5. L X Cubeddu
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Correspondence to L X Cubeddu.

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Hoffmann, I., Tavares-Mordwinkin, R., Castejon, A. et al. Endothelial nitric oxide synthase polymorphism, nitric oxide production, salt sensitivity and cardiovascular risk factors in Hispanics. J Hum Hypertens 19, 233–240 (2005). https://doi.org/10.1038/sj.jhh.1001801

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