摘要
Essential hypertension (EH) is thought to result from theinteraction of environmental and genetic factors. The molecular genetics of EH has witnessed considerable progress during the past few years. However, the number of genes involved, their chromosomal location and the magnitude of their effect on EH susceptibility are unknown. We conducted the present study to screen susceptibility genes to essential hypertension using a genome-wide scanning method in a group of Han people from Fangshan district located in the southwest of Beijing. A case-control study and affected sibpair were performed. Genotyping was carried out using a fluorescence-based semiautomated technique on automated DNA sequencer (ABI 377, PE). The basis for the genome-screen was the ABI prism linkage mapping sets of 400 microsatellite markers (version 2, PE, Co.). PCR for amplification of markers was carried out as multiplex reactions with Ampli Taq gold (PE, Co.) following protocols developed in our laboratory. Data were exported as a text file from genotyper for subsequent two-point affected sibpair linkage analysis. The data from case-control association study showed a linkage disequilibrium between EH and marker D1S249 locus (X2 = 14.6, P = 0.002). There are 12 alleles in the D1S249 locus. The frequency of A9 allele in hypertension was higher than in normotensives, (13.6% v.s. 2.7%, X2 = 6.30, p = 0.01, OR = 4.57, 95%CI = 1.24-25.4). The data from two-point affected sibpair linkage analysis demonstrated a linkage between EH and A9 allele, P＜0.05. It suggested that microsatellite marker D1S249 locus might be associated with the genetic susceptibility to essential hypertension in Han Chinese.
Essential hypertension (EH) is thought to result from the interaction of environmental and genetic factors. The molecular genetics of EH has witnessed considerable progress during the past few years. However, the number of genes involved, their chromosomal location and the magnitude of their effect on EH susceptibility are unknown. We conducted the present study to screen susceptibility genes to essential hypertension using a genome-wide scanning method in a group of Han people from Fangshan district located in the southwest of Beijing. A case-control study and affected sibpair were performed. Genotyping was carried out using a fluorescence-based semiautomated technique on automated DNA sequencer (ABI 377, PE). The basis for the genome-screen was the ABI prism linkage mapping sets of 400 microsatellite markers (version 2, PE, Co.). PCR for amplification of markers was carried out as multiplex reactions with Ampli Taq gold (PE, Co.) following protocols developed in our laboratory. Data were exported as a text file from genotyper for subsequent two-point affected sibpair linkage analysis. The data from case-control association study showed a linkage disequilibrium between EH and marker D1S249 locus (X2 = 14.6, P = 0.002). There are 12 alleles in the D1S249 locus. The frequency of A9 allele in hypertension was higher than in normotensives, (13.6% v.s. 2.7%, X2 = 6.30, p = 0.01, OR = 4.57, 95%CI = 1.24-25.4). The data from two-point affected sibpair linkage analysis demonstrated a linkage between EH and A9 allele, P<0.05. It suggested that microsatellite marker D1S249 locus might be associated with the genetic susceptibility to essential hypertension in Han Chinese.
基金
China Medical Board of New York, Inc. (96-657) and National Natural Science Foundation of China (Grant No. 39870687).
