Department of Cardiology, The 85th Hospital of PLA, 1328 Huashan Road, Shanghai, 200052, People's Republic of China.
Mol Biol Rep. 2013 Jun;40(6):4001-8. doi: 10.1007/s11033-012-2478-y. Epub 2013 Jan 1.
Monocyte differentiation antigen CD14 is considered an important cell-activating mediator of inflammatory responses that may result in atherosclerosis, coronary heart disease (CHD), thrombus formation, and myocardial infarction (MI). A common C-260T polymorphism in the promoter of the CD14 gene, the trans-membrane receptor of lipopolysaccharides, has been inconsistently associated with CHD. To investigate this inconsistency, we performed a meta-analysis of 28 studies involving a total of 13,335 CHD cases and 7,979 controls for C-260T of the CD14 gene to evaluate the effect of CD14 on genetic susceptibility for CHD. An overall random effects odds ratio of 1.24 (95 % CI: 1.12-1.36, P < 10(-5)) was found for T allele. Significant results were also observed using dominant (OR = 1.34, 95 % CI: 1.17-1.54, P < 10(-4)) or recessive genetic model (OR = 1.25, 95 % CI: 1.10-1.41, P = 0.0004). There was strong evidence of heterogeneity (P < 10(-5)), which largely disappeared after stratification by ethnicity. After stratified by ethnicity, significant results were found in East Asians; whereas no significant associations were found among Caucasians and other ethnic populations in all genetic models. In the stratified analysis according to sample size, CHD endpoints, and HWE status, significantly increased risks for the polymorphism were found in all genetic models. In conclusion, our results indicate that the CD14 C-260T polymorphism is a risk factor of CHD, especially in East Asians. However, additional very large-scale studies are warranted to confirm our results.
单核细胞分化抗原 CD14 被认为是炎症反应的重要细胞激活介质,可能导致动脉粥样硬化、冠心病(CHD)、血栓形成和心肌梗死(MI)。CD14 基因启动子中的常见 C-260T 多态性是脂多糖的跨膜受体,与 CHD 的相关性不一致。为了研究这种不一致性,我们对 28 项研究进行了荟萃分析,这些研究共包括 13335 例 CHD 病例和 7979 例对照,以评估 CD14 基因 C-260T 对 CHD 遗传易感性的影响。总体随机效应比值比为 1.24(95%可信区间:1.12-1.36,P<10(-5))。采用显性(OR=1.34,95%可信区间:1.17-1.54,P<10(-4))或隐性遗传模型(OR=1.25,95%可信区间:1.10-1.41,P=0.0004)也观察到显著结果。存在显著的异质性(P<10(-5)),按种族分层后大部分异质性消失。按种族分层后,在东亚人群中发现了显著的结果;而在白种人和其他种族人群中,所有遗传模型均未发现显著相关性。在按样本量、CHD 终点和 HWE 状态分层的分析中,所有遗传模型均发现该多态性显著增加了风险。总之,我们的研究结果表明,CD14 C-260T 多态性是 CHD 的一个危险因素,尤其是在东亚人群中。然而,需要进行更大规模的研究来证实我们的结果。