MALAT1 多态性与中国人群冠心病风险的关联。
Association of polymorphisms in MALAT1 with risk of coronary atherosclerotic heart disease in a Chinese population.
机构信息
Department of Heart Vascular Surgery, Yan'An Hospital Affiliated to Kunming Medical University, Kunming, 650051, Yunnan, People's Republic of China.
出版信息
Lipids Health Dis. 2018 Apr 10;17(1):75. doi: 10.1186/s12944-018-0728-2.
BACKGROUND
Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) plays an important role in vascular remodeling. Down-regulation of MALAT1 can inhibit the proliferation of vascular endothelial cells and vascular smooth muscle cells, reduce cardiomyocyte apoptosis and improve left ventricular function, which is closely linked to numerous pathological processes such as coronary atherosclerotic heart disease (CAD). The aim of this study was to investigate whether polymorphisms in MALAT1 were associated with the susceptibility to CAD.
METHODS
A total of 508 CAD patients and 562 age-, gender-, and ethnicity-matched controls were enrolled in this study. Four polymorphisms in MALAT1 (i.e., rs11227209, rs619586, rs664589, and rs3200401) were genotyped using a TaqMan allelic discrimination assay.
RESULTS
The rs619586 AG/GG genotypes and G allele were associated with a reduced risk of CAD (AG/GG vs. AA: adjusted OR = 0.66, 95% CI: 0.48-0.91; G vs. A: adjusted OR = 0.68, 95% CI: 0.51-0.90). Stratification analyses showed that CAD patients with rs11227209 CG/GG, rs619586 AG/GG, and rs3200401 CT/TT genotypes exhibited lower levels of TCH (P = 0.02, 0.04, and 0.02, respectively). Moreover, CGCC haplotype was associated with a decreased risk of CAD (OR = 0.28, 95% CI: 0.16-0.48). Multivariate logistic regression analysis identified some independent risk factors for CAD, including rs619586 and rs664589. Subsequent combined analysis showed that the combined genotypes of rs619586AG/GG and rs664589CC were associated with a reduced risk of CAD (OR = 0.29; 95%CI, 0.16-0.53).
CONCLUSIONS
These findings indicate that rs619586AG/GG genotypes in MALAT1 may protect against the occurrence of CAD.
背景
转移相关肺腺癌转录物 1（MALAT1）在血管重塑中发挥重要作用。下调 MALAT1 可以抑制血管内皮细胞和血管平滑肌细胞的增殖，减少心肌细胞凋亡，改善左心室功能，与冠状动脉粥样硬化性心脏病（CAD）等许多病理过程密切相关。本研究旨在探讨 MALAT1 多态性是否与 CAD 的易感性相关。
方法
本研究共纳入 508 例 CAD 患者和 562 名年龄、性别和种族匹配的对照。采用 TaqMan 等位基因鉴别分析检测 MALAT1 中的 4 个多态性（即 rs11227209、rs619586、rs664589 和 rs3200401）。
结果
rs619586AG/GG 基因型和 G 等位基因与 CAD 风险降低相关（AG/GG 与 AA：调整后的 OR=0.66，95%CI：0.48-0.91；G 与 A：调整后的 OR=0.68，95%CI：0.51-0.90）。分层分析显示，rs11227209CG/GG、rs619586AG/GG 和 rs3200401CT/TT 基因型的 CAD 患者的 TCH 水平较低（P=0.02、0.04 和 0.02）。此外，CGCC 单倍型与 CAD 风险降低相关（OR=0.28，95%CI：0.16-0.48）。多变量 logistic 回归分析确定了 CAD 的一些独立危险因素，包括 rs619586 和 rs664589。随后的联合分析显示，rs619586AG/GG 和 rs664589CC 的联合基因型与 CAD 风险降低相关（OR=0.29；95%CI，0.16-0.53）。
结论
这些发现表明 MALAT1 中的 rs619586AG/GG 基因型可能有助于预防 CAD 的发生。
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