Yun Yan, Ma Chi, Ma XiaoChun
School of Medicine, Shandong University, Ji'nan, Shandong, People's Republic of China.
PLoS One. 2014 May 14;9(5):e97289. doi: 10.1371/journal.pone.0097289. eCollection 2014.
The complications of atherosclerosis such as coronary and cerebrovascular disease, are the most prevalent causes of mortality and morbidity worldwide. A single nucleotide polymorphism (SNP) rs1883832 (-1C/T) in CD40 gene has been recently suggested to contribute to the susceptibility to atherosclerosis in Chinese population; however, previous genetic association studies yielded inconsistent results.
A meta-analysis of eligible studies reporting the association between rs1883832 and atherosclerosis in Chinese population was carried out.
Pooling 7 eligible case-control studies involving 2129 patients and 1895 controls demonstrated a significant association between rs1883832 and atherosclerosis under dominant model [odds ratio (OR) = 1.631, 95% confidence interval [CI] [1.176, 2.260] in Chinese population with evident heterogeneity. Meta-regression analysis indicated that the heterogeneity could be completely explained by disease category. In subgroup analysis, rs1883832 conferred ORs of 2.866 (C/C versus T/T, 95%CI [2.203, 3.729]) and 1.680 (C/T versus T/T, 95%CI [1.352, 2.086]) for coronary artery disease (CAD) under co-dominant model without heterogeneity. Similar results were obtained for acute coronary syndrome (ACS) (C/C versus T/T, 3.674, 95%CI [2.638, 5.116]; C/T versus T/T, 1.981, 95%CI [1.483, 2.646]). The other genetic models including dominant, recessive and additive models, yielded consistent results without heterogeneity for CAD and ACS, respectively. However, a protective role was found for C allele in ischemic stroke (IS) under recessive model (0.582, 95%CI [0.393, 0.864]) and additive model (0.785, 95%CI [0.679, 0.909]) with reduced heterogeneity.
This meta-analysis provided evidence of association of rs1883832 C allele with an overall increased risk of atherosclerosis but distinct effect of C allele on CAD (including ACS) and IS in Chinese population, respectively.
动脉粥样硬化的并发症,如冠心病和脑血管疾病,是全球范围内最常见的死亡和发病原因。最近有研究表明,CD40基因中的单核苷酸多态性(SNP)rs1883832(-1C/T)与中国人群动脉粥样硬化易感性有关;然而,以往的基因关联研究结果并不一致。
对报道rs1883832与中国人群动脉粥样硬化关联的合格研究进行荟萃分析。
汇总7项合格的病例对照研究,涉及2129例患者和1895例对照,结果显示在显性模型下,rs1883832与中国人群动脉粥样硬化存在显著关联[优势比(OR)=1.631,95%置信区间(CI)[1.176,2.260],存在明显异质性。Meta回归分析表明,异质性可完全由疾病类别解释。在亚组分析中,在共显性模型下,rs1883832对于冠心病(CAD)的OR值分别为2.866(C/C与T/T相比,95%CI[2.203,3.729])和1.680(C/T与T/T相比,95%CI[1.352,2.086]),无异质性。急性冠状动脉综合征(ACS)也得到了类似结果(C/C与T/T相比,3.674,95%CI[2.638,5.116];C/T与T/T相比,1.981,95%CI[1.483,2.646])。包括显性、隐性和加性模型在内的其他遗传模型,分别在CAD和ACS中得到了无异质性的一致结果。然而,在隐性模型(0.582,95%CI[0.393,0.864])和加性模型(0.785,95%CI[0.679,0.909])下,发现C等位基因对缺血性卒中(IS)具有保护作用,异质性降低。
这项荟萃分析提供了证据,表明rs1883832的C等位基因与中国人群动脉粥样硬化总体风险增加有关,但C等位基因对CAD(包括ACS)和IS的影响分别不同。