内皮细胞和平滑肌细胞中表达的基因功能多态性与心肌梗死的关系。

The association of functional polymorphisms in genes expressed in endothelial cells and smooth muscle cells with the myocardial infarction.

机构信息

Department of Cardiology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.

Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin Medical University, Harbin, 150001, China.

出版信息

Hum Genomics. 2019 Jan 24;13(1):5. doi: 10.1186/s40246-018-0189-8.

DOI:10.1186/s40246-018-0189-8

PMID:30678728

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6345039/

Abstract

BACKGROUND

The association of platelet endothelial cell adhesion molecule 1 (PECAM1), hypoxia-inducible factor 1 subunit alpha (HIF1A), and KIAA1462 in myocardial infarction (MI) was investigated. The study included 401 Han Chinese MI patients and 409 controls. Three tag single-nucleotide polymorphisms (SNPs)-PECAM1 rs1867624, HIF1A rs2057482, and KIAA1462 rs3739998-were selected. SNP genotyping was performed by an improved multiplex ligation detection reaction assay. A systematic review and meta-analysis of studies including 3314 cases and 2687 controls on the association of 5 HIF1A SNPs and the overall risk of MI or coronary artery disease (CAD) was performed.

RESULTS

The rs1867624 variants were associated with high TG concentrations (p = 0.040) and the rs2057482 variants were associated with decreased HDL-C in MI patients compared with the control group (p = 0.003). Rs2057482 SNP interacted with age to influence TC levels. The SNP of rs3739998 interacted with sex and hypertension to modulate CRE and TG levels, respectively (p < 3.04E-5-0.002). No association between the three SNPs and susceptibility to MI was found (p > 0.05 for all). In the meta-analysis of HIF1A, the rs11549465 C > T and rs10873142 T > C polymorphisms, but not rs2057482, rs11549467, and rs41508050, were correlated with overall MI or CAD risk.

CONCLUSIONS

Taken together, this study provides additional evidence that genetic variation of the PECAM1 rs1867624 and HIF1A rs2057482 can mediate lipid levels in MI patients.

摘要

背景

本研究旨在探讨血小板内皮细胞黏附分子 1（PECAM1）、缺氧诱导因子 1 亚基α（HIF1A）和 KIAA1462 在心肌梗死（MI）中的相关性。该研究纳入了 401 名汉族 MI 患者和 409 名对照。选择了 3 个标签单核苷酸多态性（SNP）-PECAM1 rs1867624、HIF1A rs2057482 和 KIAA1462 rs3739998。采用改良多重连接检测反应检测 SNP 基因型。对纳入 3314 例病例和 2687 例对照的关于 5 个 HIF1A SNP 与 MI 或冠心病（CAD）总体风险相关性的研究进行了系统评价和荟萃分析。

结果

与对照组相比，rs1867624 变异与 MI 患者的高甘油三酯（TG）浓度相关（p=0.040），rs2057482 变异与高密度脂蛋白胆固醇（HDL-C）降低相关（p=0.003）。rs2057482 与年龄相互作用影响 TC 水平。rs3739998 与性别和高血压相互作用分别调节 CRE 和 TG 水平（p<3.04E-5-0.002）。未发现这三个 SNP 与 MI 易感性相关（所有 p>0.05）。在 HIF1A 的荟萃分析中，rs11549465 C>T 和 rs10873142 T>C 多态性与总体 MI 或 CAD 风险相关，但 rs2057482、rs11549467 和 rs41508050 与总体 MI 或 CAD 风险无关。