Gu Dongfeng, Ge Dongliang, Snieder Harold, He Jiang, Chen Shufeng, Huang Jianfeng, Li Biao, Chen Runsheng, Qiang Boqin
Division of Population Genetics and Prevention, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
J Hypertens. 2006 Jun;24(6):1049-56. doi: 10.1097/01.hjh.0000226194.21311.2f.
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 alpha1A adrenergic receptor (ADRA1A) gene, located on chromosome 8p21-p11.2, with essential hypertension in a northern Han Chinese population.
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.
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.
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.
我们之前报道了人类8号染色体p22区域与原发性高血压及收缩压水平之间存在显著连锁关系。基于此，我们采用了一种有效的年龄、性别和地区匹配的病例对照方案，来检测位于8号染色体p21 - p11.2区域的人类α1A肾上腺素能受体（ADRA1A）基因多态性与中国北方汉族人群原发性高血压的关联。
通过对随机招募的48例高血压患者和48例健康受试者的基因组DNA进行直接测序，鉴定出7种多态性。还对480例2期高血压患者及其个体匹配的对照进行了这些多态性与原发性高血压关联的检测。
我们观察到病例组中347Arg等位基因和2547G等位基因的频率显著高于对照组（P值分别为0.04和0.007）。McNemar检验显示，携带2547G等位基因的个体患原发性高血压的风险更高，优势比为3.00 [95%置信区间（CI）1.23 - 8.35]。然后我们进行了条件逻辑回归以调整传统危险因素的影响，结果显示携带2547G等位基因的个体优势比为2.84（95% CI 1.15 - 6.99）。使用PHASE软件估计单倍型概率后，我们进行了单倍型趋势回归分析，结果显示在调整传统危险因素后，单倍型7与原发性高血压之间存在显著关联（P = 0.02）。
我们的研究结果表明，ADRA1A基因的遗传变异与原发性高血压显著相关，可能在该中国人群原发性高血压的发生发展中起重要作用。
