Essential hypertension may be determined by just a few genes

As part of the British Genetics of Hypertension (BRIGHT) study, which aims to identify genes that confer susceptibility to essential hypertension through a genome-wide linkage screen, the researchers phenotyped and genotyped 2010 affected sibling pairs drawn from 1599 severely hypertensive families. Each family taking part in the study contained at least two affected siblings, in whom the onset of hypertension had been diagnosed before the age of 60 years, and who had a sitting blood pressure (BP) of 150/100 mmHg or higher at one reading, or 145/95 mmHg at three readings. Caulfield et al identified one chromosomal region, 6q, with a lod score of more than 3.14. In addition, three other regions, 2q, 5q, and 9q, had lod scores higher than 1.57. "Computer simulations for a locus-counting analysis suggest that these linkages collectively attain genome-wide significance (p=0.017)," the researchers report. After excluding sibling pairs in whom one or more siblings had a body mass index of 30 kg/m2 or more, the maximum lod scores for chromosomes 6, 5, and 9 remained relatively unchanged, but the lod score for chromosome 2q dropped to 0.98. The fourth largest maximum lod score, of 1.78, for this new analysis was mapped on to chromosome 8. The authors conclude that their findings imply that human essential hypertension has an oligogenic element (a few genes may be involved in determination of the trait) possibly superimposed on more minor genetic effects, and that several genes may be tractable to a positional cloning strategy. "The potential of our results might be the discovery of previously unrecognized biochemical pathways, or processes as the root cause of this major risk factor for cardiovascular disease" they add.In an editorial accompanying the study in The Lancet, Stephen Harrap (University of Melbourne) commented that instead of genetic searches for the whereabouts of every allele controlling BP, a search is needed for molecular clues to the common physiological mechanisms underlying disease. By strengthening the bridges between molecular and integrative biological sciences," he writes. "Then, genetics will fulfill its promise." Reference...