Published Online
on August 28, 2006

A more recent version of this article appeared on October 1, 2006

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Submitted on April 9, 2006
Revised on May 4, 2006

Endothelial NO Synthase Gene Polymorphisms and Hypertension. A Meta-Analysis

Elias Zintzaras^*; Georgios Kitsios; and Ioannis Stefanidis

From the Department of Biomathematics (E.Z., G.K.), and Department of Nephrology (I.S.), University of Thessaly School of Medicine, Larissa, Greece.

^* To whom correspondence should be addressed. E-mail: zintza{at}med.uth.gr.

Abstract--Studies investigated the association between endothelial NO synthase gene polymorphisms and hypertension-reported contradicted or nonconclusive results. A meta-analysis of 35 genetic association studies that examined the relation between hypertension and the G894T, 4a/b, T786C, and G23T polymorphisms of the endothelial nitric oxide synthase gene was carried out. Subgroup analysis by ethnicity and potential sources of heterogeneity and bias were explored. The meta-analysis included genotype data on 7779/10 498, 2216/3222, 2491/3913, and 833/587 cases/controls for G894T, 4b/a, T786C, and G23T, respectively. For the 4b/a polymorphism, overall, the heterogeneity between studies was not significant (P=0.82), and the allele b was associated with a 15% decreased risk of hypertension relative to allele a (odds ratio: 0.85; 95% CI: 0.74 to 0.98). Overall and in whites, the recessive model for allele b produced significant results (odds ratios: 0.78; 95% CI: 0.68 to 0.90 and OR: 0.76 95% CI: 0.62 to 0.92, respectively), whereas the dominant model produced nonsignificant results. In studies involved East Asians and blacks, an association was not demonstrated. Regarding the G894T, T768C, and G23T polymorphisms, in no case (ie, overall, in whites, or in East Asians) was a statistically significant association and heterogeneity found. There was no substantial source of bias in the selected studies. In conclusion, there is evidence of association only between 4b/a polymorphism and hypertension; however, studies exploring combinations of the polymorphisms may help us better understand the genetics of hypertension.

Key words: nitric oxide • polymorphism • meta-analysis

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