LACK OF EVIDENCE FOR LINKAGE OF THE ENDOTHELIAL-CELL NITRIC-OXIDE SYNTHASE GENE TO ESSENTIAL-HYPERTENSION

Background The basal release of nitric oxide by the endothelium plays an important role in regulating blood flow and pressure and mediates m ost of the endothelium-dependent vasodilation. Impairment of nitric ox ide production by specific inhibitors increases blood pressure in huma ns, and several reports suggest that hypertensive subjects have a blun ted endothelium-dependent vasodilatation that might be secondary to de creased nitric oxide production from the vessel wall. Methods and Resu lts To determine whether the endothelial nitric oxide synthase gene is involved in human essential hypertension, we identified informative b iallelic and multiallelic markers of this locus and performed case-con trol and linkage studies in hypertensive subjects and normotensive con trol subjects. We used the affected sib pair method to test for potent ial linkage in 145 hypertensive pedigrees (269 sib pairs, 346 subjects ) with a highly polymorphic marker of the nitric oxide synthase gene ( polymorphism information content of 92%). There was no evidence for li nkage among affected siblings. The 95% upper confidence limit of this value suggests that at most 1% of alleles in excess of expected are sh ared. We also identified two informative biallelic markers of this gen e to perform a case-control study on white hypertensive and normotensi ve subjects. Similar genotype distributions between the two groups wer e noted for both markers. Estimated haplotype frequencies by maximum l ikelihood methods combining the two biallelic markers were also simila r in both groups. Conclusions These findings do not suggest that commo n molecular variants of the endothelial nitric oxide synthase gene are involved in essential hypertension.