Original Article

Journal of Molecular Medicine

, Volume 85, Issue 8, pp 877-885

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

  • Qi ZhaoAffiliated withDepartment of Evidence Based Medicine and Division of Population Genetics, Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeNational Human Genome Center at Beijing
  • , Zhongjie FanAffiliated withDepartment of Cardiology, Peking Union Medical College Hospital
  • , Jiang HeAffiliated withTulane University Medical Center
  • , Shufeng ChenAffiliated withDepartment of Evidence Based Medicine and Division of Population Genetics, Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
  • , Hongfan LiAffiliated withDepartment of Evidence Based Medicine and Division of Population Genetics, Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
  • , Penghua ZhangAffiliated withDepartment of Evidence Based Medicine and Division of Population Genetics, Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
  • , Laiyuan WangAffiliated withDepartment of Evidence Based Medicine and Division of Population Genetics, Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
  • , Dongsheng HuAffiliated withDepartment of Epidemiology, College of Public Health, Zhengzhou University
  • , Jianfeng HuangAffiliated withDepartment of Evidence Based Medicine and Division of Population Genetics, Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
    • , Boqin QiangAffiliated withNational Human Genome Center at Beijing
    • , Dongfeng GuAffiliated withDepartment of Evidence Based Medicine and Division of Population Genetics, Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeNational Human Genome Center at Beijing Email author 

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Abstract

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.

Keywords

Case-control studies Hypertension Kidney Monoamine oxidase Single nucleotide polymorphism