Chromosome 17 and the inducible nitric oxide synthase gene in human essential hypertension

Essential hypertension is a common multifactorial trait that results in a s ignificantly increased risk for heart attack and stroke. The condition has a genetic basis, although at present the number of genes is unknown. In ord er to identify such genes, we are utilising a linkage scanning approach usi ng microsatellite markers and affected sibships. Here we provide evidence f or the location of at least one hypertension susceptibility locus on chromo some 17. Analysis of 177 affected sibpairs gave evidence for significant ex cess allele sharing to D17S949 (SPLINK: P=0.0029; MAPMAKER SIBS: P=0.0033; ASPEX: P=0.0061; GENEHUNTER: P=0.0096, ANALYZE (SIBPAIR): P=0.0025) on 17q2 2-24, with significant allele sharing also indicated for an additional mark er, D17S799 (SPLINK: P=0.025, MAPMAKER SIBS: P= 0.025) located close to the centromere. Since these two genomic regions are well separated, our result s indicate that there may be more than one chromosome 17 locus affecting hu man blood pressure. Moreover, further investigation of this chromosome, uti lizing a polymorphism within the promoter of the iNOS candidate gene, NOS2A , revealed both increased allele sharing among sibpairs (SPLINK: P=0.02; AS PEX: P=0.00004) and positive association (P= 0.034) of NOS2A to essential h ypertension. Hence these results indicate that chromosome 17 and. more spec ifically, the NOS2A gene may play a role in human essential hypertension.