Renalase gene is a novel susceptibility gene for essential hypertension: a two-stage association study in northern Han Chinese population
Renalase gene is a novel susceptibility gene for essential hypertension: a two-stage association study in northern Han Chinese population
复制标题
肾酶基因是本质性高血压的新型易感基因：对中国北方汉族人群的两阶段关联研究
DOI：
10.1007/s00109-006-0151-4
复制
发表时间：
2007-08-01
影响因子：
4.7
通讯作者：
Gu, Dongfeng
中科院分区：
文献类型：
--
作者：
Zhao, Qi;Fan, Zhongjie;Gu, Dongfeng
Renalase是一种新的黄素腺嘌呤二核苷酸依赖的胺氧化酶，由肾脏分泌，降解循环儿茶酚胺，调节心功能和全身血压（BP）。它的发现可能为血压调节机制和原发性高血压（EH）的发病机制提供新的见解。我们设计了一项两阶段的病例对照研究，以调查中国北方汉族人群中renalase基因是否存在与EH相关的遗传变异。从亚洲心血管疾病国际合作研究（InterASIA in China）中招募了1317例高血压病例和1269例正常对照。本研究以这2586名受试者为主要研究人群。在第1阶段，在主要研究人群的一个亚样本（503例病例和490例对照）中，对所有8个选择的renalase基因单核苷酸多态性（snp）进行基因分型和检测。单位点分析显示，rs2576178、rs2296545和rs2114406与EH有显著相关性（P < 0.05）。在第二阶段，这三个snp在剩余个体上进行基因分型，并使用所有个体进行分析。经多次比较Bonferroni校正后，rs2576178和rs2296545与EH的相关性在2期仍然显著。rs2576178 G等位基因和rs2296545 C等位基因频率高于对照组（0.55比0.49,P < 0.0001； 0.61比0.55,P < 0.0001）。特别是在共显性模型下，rs2576178 GG基因型和rs2296545 CC基因型的校正优势比分别为1.58 （95% CI, 1.25 ~ 2.00， P=0.0002）和1.61 （95% CI, 1.26 ~ 2.04， P=0.0002）。我们还发现了风险相关的单倍型和双倍型，这进一步证实了renalase基因与EH之间的显著关联。这些发现可能为EH提供新的遗传易感性标记，并有助于更好地了解EH的病理生理。此外，还需要在其他人群和功能研究中进行进一步的重复研究。
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.