A quantitative trait locus for SBP maps near KCNB1 and PTGIS in a population isolate

Population isolates are characterized by simplified genetic background and as such present promising opportunities for studying complex diseases. We performed a genome-wide linkage analysis for systolic (SBP) and diastolic blood pressure (DBP) followed up by the association analysis in the Croatian isolated island of Vis, where a very high prevalence of hypertension was reported (75%).

Variance-components linkage analysis was used to map quantitative trait loci (QTL) for SBP and DBP in 125 families with 1,389 members. Follow-up association analysis was performed in a sample of 421 subjects from the island of Vis. The 15 top-ranking single nucleotide polymorphisms (SNPs) were selected and tested for the association by in silico replication in the British 1958 Birth Cohort DNA Collection.

Linkage results showed evidence for a QTL influencing DBP (lod = 1.89) on chromosome 7p14.2 and two QTL influencing SBP (lod = 2.03 on chromosome 1p36 and lod = 1.75 on chromosome 20q13). For the association results, the replication was observed for the rs237484 polymorphism on chromosome 20 that was associated with SBP with the effect size beta = -5.2 (P = 0.001; per A allele) in Vis population and beta = -1.1 (P = 0.04) in the British 1958 Birth Cohort. rs237484 is in proximity to the potassium voltage gate channel gene (KCNB1) and close to the prostaglandin I2 (prostacyclin) synthase gene (PTGIS).

These results provide evidence of a QTL influencing blood pressure (BP) variability in this region and support the notion that the isolated population of the island of Vis is a suitable population for conducting linkage and association analyses of cardiovascular-related phenotypes.