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新疆南部地区ACE2基因多态性与高血压相关靶器官损害的关联

Association of ACE2 genetic polymorphisms with hypertension-related target organ damages in south Xinjiang.

作者信息

Luo Yi, Liu Cheng, Guan Tianwang, Li Yanfang, Lai Yanxian, Li Fang, Zhao Haiyan, Maimaiti Tutiguli, Zeyaweiding Abudurexiti

机构信息

Department of Cardiology, Guangzhou First People's Hospital, Medical School, South China University of Technology, 510180, Guangzhou, China.

Department of Cardiology, Guangzhou First People's Hospital, Guangzhou Medical University, 510180, Guangzhou, China.

出版信息

Hypertens Res. 2019 May;42(5):681-689. doi: 10.1038/s41440-018-0166-6. Epub 2018 Dec 12.

Abstract

Essential hypertension (EH) is a principal contributing factor in worldwide cardiovascular disease mortality. Although interventions that minimize environmental risk factors for EH are associated with reduced cardiovascular disease, such approaches are limited for individuals with high genetic EH risk. In this study, we investigated possible associations between ACE2 polymorphisms and hypertension-related target organ damages in south Xinjiang, China. Four hundred and two hypertensive patients were enrolled as study participants in an EH group, and 233 normotensive individuals were enrolled as control subjects. Participants were recruited from the south Xinjiang region. Fourteen ACE2 polymorphisms were genotyped by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Risk genotypes of rs2074192 (TT+CT, OR = 1.72, 95% CI: 1.17-2.53), rs2106809 (TT, OR = 1.71, 95% CI: 1.13-2.58), rs4240157 (CC+CT, OR = 1.99, 95% CI: 1.17-3.41), rs4646155 (TT+CT, OR = 1.94, 95% CI: 1.06-3.54), rs4646188 (TT+CT, OR = 3.25, 95% CI: 1.95-5.41), rs4830542 (CC+CT, OR = 1.88, 95% CI: 1.10-3.23), and rs879922 (CC+CG, OR = 4.86, 95% CI: 2.74-8.64) were associated with EH. Hypertensive patients carrying the control genotype of rs2074192 (CC, OR = 2.37, 95% CI: 1.28-4.39) were associated with CAS ≥50%, while those carrying a high-EH-risk genotype of rs4240157 (OR = 2.62, 95% CI: 1.24-5.54), rs4646155 (OR = 2.44, 95% CI: 1.16-5.10), or rs4830542 (CC+CT, OR = 2.20, 95% CI: 1.03-4.69) were associated with atrial fibrillation (AF), larger left atrial diameter, and higher levels of renin-angiotensin-aldosterone system (RAAS) activation (renin and angiotensin I/II). In conclusion, the ACE2 variant rs2074192 was associated with EH and EH with CAS ≥50%, while 3 ACE2 variants (rs4240157, rs4646155, and rs4830542) were associated with EH- and hypertension-related AF and left atrial remodeling in south Xinjiang, China.

摘要

原发性高血压(EH)是全球心血管疾病死亡的主要促成因素。尽管将EH的环境风险因素降至最低的干预措施与心血管疾病的减少有关,但对于具有高遗传EH风险的个体来说,这些方法是有限的。在本研究中,我们调查了中国新疆南部地区ACE2基因多态性与高血压相关靶器官损害之间可能存在的关联。402例高血压患者作为EH组的研究参与者,233例血压正常个体作为对照。参与者均来自新疆南部地区。采用基质辅助激光解吸电离飞行时间质谱法对14个ACE2基因多态性进行基因分型。rs2074192(TT + CT,OR = 1.72,95%CI:1.17 - 2.53)、rs2106809(TT,OR = 1.71,95%CI:1.13 - 2.58)、rs4240157(CC + CT,OR = 1.99,95%CI:1.17 - 3.41)、rs4646155(TT + CT,OR = 1.94,95%CI:1.06 - 3.54)、rs4646188(TT + CT,OR = 3.25,95%CI:1.95 - 5.41)、rs4830542(CC + CT,OR = 1.88,95%CI:1.10 - 3.23)和rs879922(CC + CG,OR = 4.86,95%CI:2.74 - 8.64)的风险基因型与EH相关。携带rs2074192对照基因型(CC,OR = 2.37,95%CI:{1.28 - 4.39})的高血压患者与颈动脉硬化≥50%相关,而携带rs4240157(OR = 2.62,95%CI:1.24 - 5.54)、rs4646155(OR = 2.44,95%CI:1.16 - 5.10)或rs4830542(CC + CT,OR = 2.20,95%CI:1.03 - 4.69)高EH风险基因型的患者与心房颤动(AF)、较大的左心房直径以及肾素 - 血管紧张素 - 醛固酮系统(RAAS)激活水平升高(肾素和血管紧张素I/II)相关。总之,ACE2变体rs2074192与EH以及颈动脉硬化≥50%的EH相关,而3个ACE2变体(rs4240157、rs4646155和rs4830542)与中国新疆南部地区EH及高血压相关的AF和左心房重构相关。

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Relationship between genetic variants of ACE2 gene and circulating levels of ACE2 and its metabolites.
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