von Wowern Fredrik, Bengtsson Kristina, Lindgren Cecilia M, Orho-Melander Marju, Fyhrquist Frej, Lindblad Ulf, Råstam Lennart, Forsblom Carol, Kanninen Timo, Almgren Peter, Burri Philippe, Katzman Per, Groop Leif, Hulthén U Lennart, Melander Olle
Department of Endocrinology, Malmö University Hospital, SE-205 02, Malmö, Sweden.
Hum Mol Genet. 2003 Aug 15;12(16):2077-81. doi: 10.1093/hmg/ddg206.
With the aim of identifying hypertension susceptibility loci, we performed a genome wide scan in Scandinavian sib-pairs with early onset primary hypertension. To be classified as affected, a diagnosis of primary hypertension at age </=50 years was required. Two hundred and forty three patients with onset of primary hypertension at 40.0+/-7.7 (mean+/-SD) years from 91 families (91 sib-ships with a mean of 2.7 and a range of 2-6 affected members per sib-ship) were genotyped with 362 microsatellite markers with a density of approximately 10 cM. Loci obtaining nominal P</=0.016 (LOD score >/= 1.0) were fine mapped with additional markers. Multipoint non-parametric linkage analysis was performed using GENEHUNTER v 2.0. Using simulations, a nominal P</=0.0002 was determined to be a genome wide significant evidence of linkage. In the 10 cM genome wide scan, nominal P</=0.016 were found on chromosomes 1 at 81 cM (P=0.007), 2 at 115 cM (P=0.006), 3 at 108 cM (P=0.006), 14 at 45 cM (P=0.0002) and at 99 cM (P=0.001), 17 at 42 cM (P=0.015) and 19 at 89 cM (P=0.007). After fine mapping of these loci, one of the chromosome 14 loci just obtained the level of genome wide significance (P=0.0002 at 41 cM) and the chromosome 2 locus reached suggestive evidence of linkage (P=0.002 at 118 cM). Our data suggest a hypertension susceptibility locus on chromosome 14 around 41 cM. The locus on chromosome 2 is also promising as it has been implicated in hypertension and blood pressure regulation in earlier genome scans.
