title: A quantitative trait locus for SBP maps near KCNB1 and PTGIS in a population isolate.
abstract: BACKGROUND
  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%).
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute for Anthropological Research, Zagreb, Croatia. maja.barbalic@uth.tmc.edu
authors.forename: Maja
authors.initials: M
authors.lastname: Barbalić
authors.forename: Nina Smolej
authors.initials: NS
authors.lastname: Narancić
authors.forename: Tatjana
authors.initials: T
authors.lastname: Skarić-Jurić
authors.forename: Marijana Pericić
authors.initials: MP
authors.lastname: Salihović
authors.forename: Irena Martinović
authors.initials: IM
authors.lastname: Klarić
authors.forename: Lovorka Barać
authors.initials: LB
authors.lastname: Lauc
authors.forename: Branka
authors.initials: B
authors.lastname: Janićijević
authors.forename: Martin
authors.initials: M
authors.lastname: Farrall
authors.forename: Igor
authors.initials: I
authors.lastname: Rudan
authors.forename: Harry
authors.initials: H
authors.lastname: Campbell
authors.forename: Alan F
authors.initials: AF
authors.lastname: Wright
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Hastie
authors.forename: Pavao
authors.initials: P
authors.lastname: Rudan
mesh_terms: D001794:Blood Pressure / Q000502:physiology*; D017523:Croatia / Q000453:epidemiology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D008040:Genetic Linkage; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D016133:Polymerase Chain Reaction; D015995:Prevalence; D040641:Quantitative Trait Loci; D051669:Shab Potassium Channels / Q000235:genetics*; D013599:Systole
chemical_list: C496988:KCNB1 protein, human; D051669:Shab Potassium Channels; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; C472456:PTGIS protein, human