miR-27a rs895819 多态性与中国汉族人群心肌梗死风险的关联。
The association between pre-miR-27a rs895819 polymorphism and myocardial infarction risk in a Chinese Han population.
机构信息
Institute of Aging Research, Guangdong Medical University, Xin Cheng Avenue 1#, Songshan Lake, Dongguan, 523808, People's Republic of China.
Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan, People's Republic of China.
出版信息
Lipids Health Dis. 2018 Jan 6;17(1):7. doi: 10.1186/s12944-017-0652-x.
BACKGROUND
Accumulating evidences have shown that miRNAs are directly or indirectly involved in a variety of biological processes, and closely associated with diverse human diseases, including cardiovascular diseases. SNPs locating within pri/pre-miRNA can affect miRNA processing and binding ability of target genes. MiR-27a, miR-26a-1 miR-100, miR-126 and miR-218 were reported to be associated with pathogenesis of myocardial infarction (MI). Here we aimed to evaluate the potential association of five polymorphisms in these pri/pre-miRNAs with individual susceptibility to MI in a Chinese Han population.
METHODS
Genotyping was performed in 287 MI cases and 646 control subjects using polymerase chain reaction-ligase detection reaction (PCR-LDR) method. The association of these SNPs with MI risk was performed with SPSS software.
RESULTS
In a logistic regression analysis, we found that AG heterozygote (OR = 0.40, 95% CI = 0.21-0.76, Pa = 0.005) or AA homozygote (OR = 0.40, 95% CI = 0.22-0.75, Pa = 0.004) of pre-miR-27a rs895819 had a reduced susceptibility to MI in comparison with GG homozygote. Similarly, a reduced risk of MI was detected when the AG and AA genotypes were combined (OR = 0.40, 95% CI = 0.22-0.74, Pa = 0.003). However, no significant association between pri-miR-26a-1 pri-miR-100, pri-miR-126 and pri-miR-218 polymorphisms and MI risk was observed under the allelic and established genetic models. Further stratified analysis of pre-miR-27a rs895819 revealed a more significant association of AG + AA genotypes with MI risk among younger, male and smoking subjects. Interestingly, AG and AA genotypes of the rs895819 polymorphism conferred about 0.17 mmol/L and 0.18 mmol/L increase in HDL-C levels compared to GG genotype.
CONCLUSIONS
Our findings suggest that the pre-miR-27a rs895819 polymorphism is associated with MI susceptibility in the Chinese Han population, which probably due to influence the HDL-C levels.
背景
越来越多的证据表明，miRNAs 直接或间接地参与了多种生物学过程，并与包括心血管疾病在内的多种人类疾病密切相关。位于 pri/pre-miRNA 内的 SNPs 可以影响 miRNA 的加工和靶基因的结合能力。已经报道 miR-27a、miR-26a-1、miR-100、miR-126 和 miR-218 与心肌梗死 (MI) 的发病机制有关。本研究旨在评估这些 pri/pre-miRNAs 中的五个多态性与中国汉族人群个体易患 MI 的潜在相关性。
方法
采用聚合酶链反应-连接酶检测反应 (PCR-LDR) 方法对 287 例 MI 病例和 646 例对照进行基因分型。使用 SPSS 软件分析这些 SNP 与 MI 风险的相关性。
结果
在逻辑回归分析中，我们发现与 GG 纯合子相比，pre-miR-27a rs895819 的 AG 杂合子 (OR=0.40, 95% CI=0.21-0.76, Pa=0.005) 或 AA 纯合子 (OR=0.40, 95% CI=0.22-0.75, Pa=0.004) 患 MI 的易感性降低。同样，当 AG 和 AA 基因型组合时，也检测到 MI 风险降低 (OR=0.40, 95% CI=0.22-0.74, Pa=0.003)。然而，在等位基因和建立的遗传模型下，未观察到 pri-miR-26a-1、pri-miR-100、pri-miR-126 和 pri-miR-218 多态性与 MI 风险之间存在显著关联。进一步对 pre-miR-27a rs895819 进行分层分析显示，在年轻、男性和吸烟人群中，AG+AA 基因型与 MI 风险的相关性更为显著。有趣的是，与 GG 基因型相比，rs895819 多态性的 AG 和 AA 基因型可使 HDL-C 水平分别升高约 0.17 mmol/L 和 0.18 mmol/L。
结论
本研究结果表明，中国汉族人群 pre-miR-27a rs895819 多态性与 MI 易感性相关，这可能与影响 HDL-C 水平有关。
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