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西班牙女性中RANK基因单核苷酸多态性与血压的关联

Association of a single nucleotide polymorphism of RANK gene with blood pressure in Spanish women.

作者信息

Pertusa Clara, Tarín Juan J, Cano Antonio, García-Pérez Miguel Angel

机构信息

Research Foundation, INCLIVA Institute of Health Research, Valencia.

Department of Cellular Biology, Functional Biology and Physical Anthropology, University of Valencia, Burjassot.

出版信息

Medicine (Baltimore). 2020 Oct 2;99(40):e22436. doi: 10.1097/MD.0000000000022436.

Abstract

In addition to governing key functions in bone metabolism and the immune system, the RANK/RANKL/OPG system plays a role in the vascular system, particularly in vascular calcification and atherosclerosis.Given that these 2 phenotypes are considered a major cause of high blood pressure (BP), in this study we analyzed the association of SNPs in RANK and OPG genes with blood pressure. An observational study was conducted of 2 SNPs in the RANK gene (rs884205 and rs78326403) and 1 in the OPG gene (rs4876869) with systolic (SBP) and diastolic blood pressure (DBP) in a cohort of 695 women.Data analysis revealed a statistically significant association between the SNP rs884205 and BP pressure (SBP and DBP). Analyzing this relationship by the dominant inheritance model for this SNP (allele risk: A), women of the AA/AC genotype showed higher BP than women of the CC genotype, both for SBP (P = .001) and for DBP (P = .003), and these associations both surpassed the Bonferroni threshold for multiple comparisons. Multivariate regression analysis including known predictors of BP as independent variables was performed to evaluate the strength of this association, which in the case of the SNP rs884205 of the RANK gene remained statistically significant after adjustment for both SBP (P = .0006) and DBP (P = .005), demonstrating the key role of this SNP in BP.We report a robust association between the SNP rs884205 in RANK gene and BP in women, and this SNP is validated as a candidate in cardiovascular risk studies.

摘要

RANK/RANKL/OPG系统除了在骨代谢和免疫系统中调控关键功能外,还在血管系统中发挥作用,尤其是在血管钙化和动脉粥样硬化方面。鉴于这两种表型被认为是高血压的主要原因,在本研究中,我们分析了RANK和OPG基因中的单核苷酸多态性(SNP)与血压的关联。对695名女性队列中的RANK基因的2个SNP(rs884205和rs78326403)以及OPG基因的1个SNP(rs4876869)与收缩压(SBP)和舒张压(DBP)进行了观察性研究。数据分析显示,SNP rs884205与血压(SBP和DBP)之间存在统计学上的显著关联。按照该SNP的显性遗传模型(等位基因风险:A)分析这种关系,AA/AC基因型的女性在SBP(P = 0.001)和DBP(P = 0.003)方面均显示出比CC基因型的女性血压更高,并且这些关联均超过了多重比较的Bonferroni阈值。进行了以已知的血压预测因素作为自变量的多变量回归分析以评估这种关联的强度,对于RANK基因的SNP rs884205,在对SBP(P = 0.0006)和DBP(P = 0.005)进行调整后,其在统计学上仍具有显著意义,证明了该SNP在血压中的关键作用。我们报告了RANK基因中的SNP rs884205与女性血压之间存在紧密关联,并且该SNP在心血管风险研究中被验证为候选基因。

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