Genetic linkage of beta and gamma subunits of epithelial sodium channel tosystolic blood pressure

Background Mutations in the genes on chromosome 16p12 that encode the beta and gamma subunits of the epithelial sodium channel (SCNNIB and SCNNIG, res pectively) have been linked with rare sodium-dependent forms of low and hig h blood pressure. Other DNA variants in or around these genes may contribut e to variation in blood pressure and the risk of coronary heart disease and stroke. Methods We studied 286 white families from the general population in Victor ia, Australia. Each family comprised both parents and two natural children. All participants were genotyped at chromosome 16p12 by use of four highly polymorphic microsatellite markers. Quantitative phonotype measurements wer e correlated with genotype in identity-by-descent sibling-pair linkage anal yses. Findings We found significant linkage between systolic blood pressure and c hromosome 16p12 after parametric analyses (p=0.0003) and non-parametric ana lyses (p=0.001). The mean difference in systolic blood pressure between sib lings identical-by-descent at these loci was half as large (7.1 mm Hg) as t he difference between siblings non-identical at these loci (14.0 mm Hg, p=0 .001). No linkage between chromosome 16p12 and diastolic blood pressure or body-mass index was observed. Interpretation Chromosome 16p12 and the SCNNIB and SCNNIG genes are implica ted in the physiological variation of systolic blood pressure. Our findings are important in explaining individual cardiovascular risk within the gene ral population.