A systematic review and meta-analysis of 130,000 individuals shows smoking does not modify the association of APOE genotype on risk of coronary heart disease.
A systematic review and meta-analysis of 130,000 individuals shows smoking does not modify the association of APOE genotype on risk of coronary heart disease.
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DOI：
10.1016/j.atherosclerosis.2014.07.038
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发表时间：
2014-11
期刊：
影响因子：
5.3
通讯作者：
Talmud PJ
中科院分区：
文献类型：
--
作者：
Holmes MV;Frikke-Schmidt R;Melis D;Luben R;Asselbergs FW;Boer JM;Cooper J;Palmen J;Horvat P;Engmann J;Li KW;Onland-Moret NC;Hofker MH;Kumari M;Keating BJ;Hubacek JA;Adamkova V;Kubinova R;Bobak M;Khaw KT;Nordestgaard BG;Wareham N;Humphries SE;Langenberg C;Tybjaerg-Hansen A;Talmud PJ
吸烟是否是APOE基因型与冠心病（CHD）风险之间关系的效应调节因子，目前尚无明确的证据。我们检索了PubMed和EMBASE数据库，截至2013年6月11日，检索了报告APOE基因型、吸烟状况和CHD事件的已发表研究，并添加了来自人群队列的未发表数据。我们使用似然比检验检验了吸烟状态对APOE基因型与冠心病风险之间关系的影响。在总共13项研究（包括来自8个队列的未发表数据）中，确定了130，004名欧洲血统个体的10，134起CHD事件。APOE基因型（ε4携带者与非携带者）冠心病风险的比值比（OR）为1.06（95%可信区间（CI）：1.01，1.12），吸烟（现在与过去/从不吸烟者）的OR为2.05（95%CI：1.95，2.14）。当按吸烟状况分层APOE基因型与CHD的关联时，与非ε4携带者相比，ε4携带者的OR为1.11（95%可信区间：1.02，1.21），OR为1.04（95%CI 0.98，1.10）在101，215名既往/从不吸烟者中，没有证据表明效果改变（异质性P值= 0.19）。对> 60，000的个体参与者数据进行包年分析，并对心血管特征进行调整，也未能确定效果修改的证据。在迄今为止最大规模的分析中，我们没有发现吸烟状态对APOE基因型与冠心病风险之间关系的影响。我们研究了APOE基因型、吸烟和冠心病风险之间相互作用的证据。这是迄今为止对已发表和未发表数据集（> 130，000人）进行的最大荟萃分析。我们的分析没有发现相互作用的证据。这些发现使人们对APOE基因型和吸烟之间是否存在有临床意义的相互作用产生了疑问。
Conflicting evidence exists on whether smoking acts as an effect modifier of the association between APOE genotype and risk of coronary heart disease (CHD). We searched PubMed and EMBASE to June 11, 2013 for published studies reporting APOE genotype, smoking status and CHD events and added unpublished data from population cohorts. We tested for presence of effect modification by smoking status in the relationship between APOE genotype and risk of CHD using likelihood ratio test. In total 13 studies (including unpublished data from eight cohorts) with 10,134 CHD events in 130,004 individuals of European descent were identified. The odds ratio (OR) for CHD risk from APOE genotype (ε4 carriers versus non-carriers) was 1.06 (95% confidence interval (CI): 1.01, 1.12) and for smoking (present vs. past/never smokers) was OR 2.05 (95%CI: 1.95, 2.14). When the association between APOE genotype and CHD was stratified by smoking status, compared to non-ε4 carriers, ε4 carriers had an OR of 1.11 (95%CI: 1.02, 1.21) in 28,789 present smokers and an OR of 1.04 (95%CI 0.98, 1.10) in 101,215 previous/never smokers, with no evidence of effect modification (P-value for heterogeneity = 0.19). Analysis of pack years in individual participant data of >60,000 with adjustment for cardiovascular traits also failed to identify evidence of effect modification. In the largest analysis to date, we identified no evidence for effect modification by smoking status in the association between APOE genotype and risk of CHD. We examined evidence for an interaction between APOE genotype, smoking and risk of coronary heart disease. This was conducted in the largest meta-analysis of published and unpublished data sets to date (>130,000 individuals). Our analysis did not identify evidence of interaction. These findings bring into question presence of a clinically meaningful interaction between APOE genotype and smoking.