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OLR1 基因多态性与冠心病风险的关联:系统评价和荟萃分析。

Association of OLR1 gene polymorphisms with the risk of coronary artery disease: A systematic review and meta-analysis.

机构信息

Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Heart Lung. 2021 Mar-Apr;50(2):334-343. doi: 10.1016/j.hrtlng.2021.01.015. Epub 2021 Feb 1.

Abstract

BACKGROUND

Oxidized LDL receptor 1 (OLR1) encodes LOX-1, LOXIN, and OLR1D4 transcript variants. Up-regulation of LOX-1 and down-regulation of LOXIN have an essential role in causing coronary artery disease (CAD). Discovery of risk single nucleotide polymorphisms (SNPs) in OLR1 gene is clinically important as these polymorphisms could be candidate biomarkers of CAD.

OBJECTIVES

The purpose of this study is quantitative evidence synthesis on how OLR1 polymorphisms in the haplotype block impact the risk of CAD.

METHODS

First, a systematic keyword-based search in PubMed, Web of Science, and Scopus was conducted. After data extraction, pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for OLR1 polymorphisms and CAD. Twelve case-control studies, including 6,238 cases and 15,773 controls, were concluded in the meta-analysis.

RESULTS

Our findings demonstrate significant association of OLR1 polymorphisms in the haplotype block with CAD risk in all genetic models (allelic model: OR = 1.19, 95%CI = 1.06-1.34; additive model: OR = 1.54, 95%CI = 1.16-2.05; recessive model: OR = 1.26, 95%CI = 1.04-1.53; dominant model: OR = 1.28, 95%CI = 1.09-1.51). Subgroup analysis based on the type of polymorphism revealed that rs1050283 (3'UTR*188 C > T) and rs3736235 (IVS4-14 A > G) are more significantly associated with the risk of CAD compared to other polymorphisms in the haplotype block.

CONCLUSIONS

We found a significant association between OLR1 polymorphisms in the haplotype block, especially rs1050283 and rs3736235, with CAD. We also suggest that precise determination of disease association with polymorphisms in a haplotype requires investigation of all SNPs rather than a single SNP in that specific haplotype.

摘要

背景

氧化型 LDL 受体 1(OLR1)编码 LOX-1、LOXIN 和 OLR1D4 转录变体。LOX-1 的上调和 LOXIN 的下调在引起冠状动脉疾病(CAD)方面起着至关重要的作用。在 OLR1 基因中发现风险单核苷酸多态性(SNP)具有重要的临床意义,因为这些多态性可能是 CAD 的候选生物标志物。

目的

本研究的目的是对单倍型块中 OLR1 多态性如何影响 CAD 风险进行定量证据综合。

方法

首先,在 PubMed、Web of Science 和 Scopus 中进行了基于系统关键词的搜索。在数据提取后,计算了 OLR1 多态性与 CAD 之间的汇总比值比(OR)和 95%置信区间(CI)。荟萃分析包括 12 项病例对照研究,共纳入 6238 例病例和 15773 例对照。

结果

我们的研究结果表明,单倍型块中的 OLR1 多态性与 CAD 风险在所有遗传模型中均具有显著相关性(等位基因模型:OR=1.19,95%CI=1.06-1.34;加性模型:OR=1.54,95%CI=1.16-2.05;隐性模型:OR=1.26,95%CI=1.04-1.53;显性模型:OR=1.28,95%CI=1.09-1.51)。基于多态性类型的亚组分析表明,与单倍型块中的其他多态性相比,rs1050283(3'UTR*188 C>T)和 rs3736235(IVS4-14 A>G)与 CAD 风险的相关性更为显著。

结论

我们发现单倍型块中的 OLR1 多态性,特别是 rs1050283 和 rs3736235,与 CAD 之间存在显著相关性。我们还建议,精确确定疾病与特定单倍型中单个 SNP 的相关性需要调查该单倍型中的所有 SNP,而不仅仅是单个 SNP。

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