肾胺酶基因多态性与纵向血压变化和高血压发生的关联性

Association of genetic variants in renalase with longitudinal blood pressure changes and hypertension incidence

目的肾胺酶是由肾脏分泌的一种黄素蛋白胺氧化酶,通过降解循环中的儿茶酚胺发挥血压调节作用。本研究旨在分析人体肾胺酶基因多态性与远期血压变化及高血压发病的关系。方法 2004年在陕西宝鸡农村选取124个家系的515名受试者建立"盐敏感高血压研究队列",并分别于2009、2012和2018年对该队列进行长达14年的随访。采用MassARRAY检测平台对2004年采集的DNA标本进行肾胺酶基因多态性位点基因分型。结果通过14年的随访,有160名(53.9%)受试者患有高血压。肾胺酶基因多态性位点rs10887800,rs796945,rs1935582,rs2296545和rs2576178与14年的舒张压变化密切相关,而rs7922058与收缩压的变化相关。此外,基因多态性位点rs796945,rs1935582和rs2576178与随访队列14年后高血压发病显著相关。基于基因分析显示在校正多种混杂因素后,肾胺酶基因与高血压发病密切相关(PTPM =0.017)。结论肾胺酶在血压调节中发挥重要作用,并与高血压的发病显著相关。

Objective Renalase, a secretory flavoprotein with amine oxidase activity, is secreted into blood by the kidneys and is suggested to participate in catecholamine metabolism. The aim of this study was to investigate the associations of genetic variants in renalase with longitudinal blood pressure changes and hypertension incidence during 14 years of follow-up. Methods A total of 515 Chinese participants from 124 families were qualified for this study. We followed up this cohort in 2009, 2012 and 2018, respectively. Ten single nucleotide polymorphisms(SNPs) in renalase gene(RNLS) were genotyped by the MassARRAY platform. Results During 14 years of follow-up, 160(53.9%) participants developed hypertension. Renalase SNPs rs10887800, rs796945, rs1935582, rs2296545 and rs2576178 were significantly associated with 14-year change in diastolic blood pressure while SNP rs7922058 was associated with longitudinal systolic blood pressure change. In addition, SNPs rs796945, rs1935582 and rs2576178 were significantly associated with hypertension incidence over 14 years. Gene-based analysis found that renalase gene was significantly associated with hypertension incidence over 14-year follow-up(PTPM=0.017). Conclusion Renalase may play an important role in blood pressure progression and development of hypertension.