Linkage of hypertension to chromosome 2q14-q23 in Chinese families

Objectives To identify chromosome regions containing hypertension susceptib ility genes in Chinese. Subjects and methods A three-stage study was carried out in Chinese sibling s ascertained through outpatient clinics. in the first stage, 283 affected sib-pairs from 79 nuclear families were subjected to a genome-wide scan wit h 240 microsatellite marker loci. The second stage focused on chromosome 2 with additional markers resulting in an average distance of 5 cM and used a n independent sample of 637 affected sib-pairs from 161 families. In the th ird stage, a fine-scale mapping study on the suggestive region was performe d in an independent set of 777 affected sib-pairs from 106 families. Fourte en markers were used with an average distance less than 2 cM, Non-parametri c linkage analyses (NPL), parametric linkage analyses and transmission-dise quilibrium tests were used to assess evidence for linkage and association. Results Three markers (D2S168 at 27.06 cM, D2S151 at 152.04 cM and D2S142 a t 161.26 cM) on chromosome 2 with suggestive linkage to hypertension suscep tibility genes were identified in the genome-wide scan. In stage II, the su ggestive region around D2S151 and D2S142 was replicated, while the linkage around D2S168 was not, In the stage III fine-scale mapping study, multipoin t linkage analyses showed LOD scores greater than 2.0 throughout a region b etween 157.16 cM and 162.46 cM (all P < 0.001) with a maximum peak of 2.24 (P = 0.00067) at 160.52 cM. We also observed a NPL Z-score peak of 3.27 at 157.55 cM (P = 0.00086). Conclusions The results of a suggestive region on chromosome 2q14-q23 (D2S1 12-D2S2370) were consistent between each of the three studies. Interestingl y, this region overlaps a syntenic region that contains blood pressure quan titative trait loci identified in rat models of hypertension. These data su ggest that the region near D2S142 and D2S151 deserves to be further screene d for hypertension susceptibility genes. (C) 2001 Lippincott Williams & Wil kins.