Renalase gene is a novel susceptibility gene for essential hypertension: a two-stage association study in northern Han Chinese population

被引:106
作者
Zhao, Qi
Fan, Zhongjie
He, Jiang
Chen, Shufeng
Li, Hongfan
Zhang, Penghua
Wang, Laiyuan
Hu, Dongsheng
Huang, Jianfeng
Qiang, Boqin
Gu, Dongfeng
机构
[1] Chinese Acad Med Sci, Fuwai Hosp, Peking Union Med Coll, Cardiovasc Inst Dept Evidence Based Med Div PG, Beijing 100037, Peoples R China
[2] Natl Human Genome Ctr, Beijing 100176, Peoples R China
[3] Beijing Union Med Coll Hosp, Dept Cardiol, Beijing 100730, Peoples R China
[4] Tulane Univ, Med Ctr, New Orleans, LA 70112 USA
[5] Zhengzhou Univ, Coll Publ Hlth, Dept Epidemiol, Zhengzhou 450052, Peoples R China
来源
JOURNAL OF MOLECULAR MEDICINE-JMM | 2007年 / 85卷 / 08期
关键词
case-control studies; hypertension; kidney; monoamine oxidase; single nucleotide polymorphism;
D O I
10.1007/s00109-006-0151-4
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Renalase, a novel flavin adenine dinucleotide-dependent amine oxidase, is secreted by the kidney, degrades circulating catecholamines, and modulates cardiac function and systemic blood pressure (BP). Its discovery may provide novel insights into the mechanisms of BP regulation and the pathogenesis of essential hypertension (EH). We designed a two-stage case-control study to investigate whether the renalase gene harbored any genetic variants associated with EH in the northern Han Chinese population. From the International Collaborative Study of Cardiovascular Disease in Asia (InterASIA in China), 1,317 hypertensive cases and 1,269 normotensive controls were recruited. These total 2,586 subjects were taken as the main study population in this study. In stage 1, all the eight selected single nucleotide polymorphisms (SNPs) of the renalase gene were genotyped and tested within a subsample (503 cases and 490 controls) of the main study population. By single locus analyses, three SNPs, rs2576178, rs2296545, and rs2114406, showed significant associations with EH (P < 0.05). In stage 2, these three SNPs were genotyped on the remaining individuals and analyzed using all the individuals. After Bonferroni correction for multiple comparisons, the associations of rs2576178 and rs2296545 with EH were still significant in stage 2. The cases had higher frequencies of rs2576178 G allele and rs2296545 C allele than the controls (0.55 versus 0.49, P < 0.0001; 0.61 versus 0.55, P < 0.0001). Particularly, under the codominant model, the adjusted odds ratios for rs2576178 GG genotype and rs2296545 CC genotype were 1.58 (95% CI, 1.25 to 2.00; P=0.0002) and 1.61 (95% CI, 1.26 to 2.04; P=0.0002), respectively. We also found risk-associated haplotypes and diplotypes, which further confirmed the significant association between the renalase gene and EH. These findings may provide novel genetic susceptibility markers for EH and lead to a better understanding of EH pathophysiology. In addition, further replications in other populations and functional studies would be warranted.
引用
收藏
页码:877 / 885
页数:9
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