title: A new essential hypertension susceptibility locus on chromosome 2p24-p25, detected by genomewide search.
abstract: Essential hypertension (EH) is a complex disorder that results from the interaction of a number of susceptibility genes and environmental factors. We studied an isolated Sardinian village (Talana) in which the prevalence of hypertension is comparable to that in most Western populations. Talana exhibits features, such as slow demographic growth, high inbreeding, a low number of founders, stable lifestyle and culture, and accurate genealogical records, that make it suitable for the study of complex disorders. Clinical assessment of the entire adult population (N= approximately 1,000) identified approximately 100 hypertensive subjects. For our study, we selected the individuals with the most-severe EH (i.e., diastolic blood pressure >100 mm Hg), belonging to a single deep-rooted pedigree (12 generations), whose common ancestors lived in the 17th century. We performed a three-stage genomewide search using 36 affected individuals, by means of parametric linkage and allele-sharing approaches. LOD scores >1 were observed on chromosomes 1, 2, 13, 15, 17, and 19 (stage I). The most striking result was found in a 7.57-cM region on chromosome 2p24-p25. All five nonparametric linkage statistics estimated by the SimWalk2 program lie above the significance threshold of P<.008 for the whole region. Similar significance was obtained for 2p24-25 when parametric linkage (LOD score 1.99) and linkage disequilibrium mapping (P=.00006) were used, suggesting that a hypertension-susceptibility locus is located between D2S2278 and D2S168. This finding is strengthened by a recent report of linkage with marker D2S168 in a hypertensive sib-pair sample from China.
authors.affiliation: Istituto di Genetica delle Popolazioni, Consiglio Nazionale delle Ricerche, Alghero, Italy. angius@igm.ss.cnr.it
authors.forename: Andrea
authors.initials: A
authors.lastname: Angius
authors.forename: Enrico
authors.initials: E
authors.lastname: Petretto
authors.forename: Giovanni Battista
authors.initials: GB
authors.lastname: Maestrale
authors.forename: Paola
authors.initials: P
authors.lastname: Forabosco
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Casu
authors.forename: Daniela
authors.initials: D
authors.lastname: Piras
authors.forename: Manuela
authors.initials: M
authors.lastname: Fanciulli
authors.forename: Mario
authors.initials: M
authors.lastname: Falchi
authors.forename: Paola Maria
authors.initials: PM
authors.lastname: Melis
authors.forename: Mario
authors.initials: M
authors.lastname: Palermo
authors.forename: Mario
authors.initials: M
authors.lastname: Pirastu
mesh_terms: D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics*; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010375:Pedigree