Association of α1A adrenergic receptor gene variants on chromosome 8p21 with human stage 2 hypertension

被引:24
作者
Gu, Dongfeng [1 ]
Ge, Dongliang
Snieder, Harold
He, Jiang
Chen, Shufeng
Huang, Jianfeng
Li, Biao
Chen, Runsheng
Qiang, Boqin
机构
[1] Fu Wai Hosp, Chinese Acad Med Sci, Div Populat Genet & Prevent, Cardiovasc Inst, Beijing 100037, Peoples R China
[2] Peking Union Med Coll, Beijing, Peoples R China
[3] Natl Human Genome Ctr, Beijing, Peoples R China
[4] Med Coll Georgia, Georgia Prevent Inst, Dept Pediat, Augusta, GA 30912 USA
[5] Tulane Univ, Med Ctr, New Orleans, LA 70118 USA
[6] Acad Sinica, Inst Biophys, Beijing 100080, Peoples R China
关键词
epidemiology; essential hypertension; genetics; sympathetic nervous system;
D O I
10.1097/01.hjh.0000226194.21311.2f
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Objective and design We previously reported a significant linkage between human chromosome 8p22 with essential hypertension and systolic blood pressure levels. On the basis of this, we used an efficient age, sex and area-matched case-control scheme to test the association of the polymorphisms in the human alpha(1A) adrenergic receptor (ADRA1A gene, located on chromosome 8p21-p11.2, with essential hypertension in a northern Han Chinese population. Methods Seven polymorphisms were identified by direct sequencing of genomic DNA derived from 48 randomly recruited hypertensive and 48 healthy subjects. They were also examined for association with essential hypertension in 480 stage 2 hypertensive individuals and their individually matched controls. Results We observed significantly higher frequencies of the 347Arg allele and 2547G alleles in the cases compared with their controls (P = 0.04 and 0.007, respectively). McNemar's test revealed that carriers of 2547G alleles were at a greater risk of essential hypertension with an odds ratio of 3.00 [95% confidence interval (CI) 1.23-8.35]. We then performed a conditional logistic regression to adjust the effects of conventional risk factors, revealing an odds ratio of 2.84 for carriers of the 2547G allele (95% CI 1.15-6.99). With the haplotypic probabilities estimated using PHASE software, we performed haplotype trend regression analysis, showing a significant association between haplotype 7 and essential hypertension (p = 0.02), after adjustment for conventional risk factors. Conclusions Our findings suggest that the genetic variations in the ADRA1A gene are significantly associated with essential hypertension, and may play an important role in the development of essential hypertension in this Chinese population.
引用
收藏
页码:1049 / 1056
页数:8
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