Genome-Wide Scan for Premature Hypertension Supports Linkage to Chromosome 2 in a Large Kyrgyz Family

We report a genome-wide scan for susceptibility loci to hypertension in a single Kyrgyz family where 10 of the affected relatives developed hypertension before the age of 35 years, and some members have suffered stroke. The early onset of disease and the geographic isolation of the Kyrgyz population are both expected to select for an increased influence of genetic factors in hypertension. We genotyped 44 individuals from this Krygyz family with 374 microsatellite markers, covering a 10-centimorgan map. Nonparametric analysis suggests that affected status is linked to loci in the chromosome 2q23 to q37 genomic interval, whereas 2-point parametric analysis returned a logarithm of odds score of 2.67 for marker D2S2330 (2q24.3). Multipoint linkage analysis substantiated the evidence for a hypertension susceptibility allele in the chromosome 2q23 to q36 region. Fine mapping and haplotype analysis implicate that the genetic lesion resides between markers D2S2380 (166.5 cM) and D2S335 (175.9 cM). This finding supports other recent studies of early onset hypertension suggesting that the region 2q24.3 to q31.1 encompasses a novel locus for premature hypertension.