冠心病易感基因载脂蛋白E、低密度脂蛋白受体多态性与烟、酒的交互作用的研究

目的　探讨载脂蛋白E(ApoE)、低密度脂蛋白受体 (LDL R)基因多态性与烟、酒对汉族人群冠心病的交互影响。方法　采用病例 -对照研究方法 ,ApoE基因多态性检测用多重特异性扩增突变系统快速分型法 ,LDL R基因AvaⅡ位点多态性采用多聚酶链反应 限制性片段长度多态性 ,血脂测定在全自动化分析仪上进行 ,资料分析用Logistic回归模型等。病例组 14 6人 ,平均年龄6 4岁±11岁 ;对照组 340人 ,平均年龄 6 3岁± 12岁。结果　 (1)病例组收缩压和舒张压 (132mmHg± 2 1mmHg ,81mmHg± 13mmHg ,1mmHg =0 133kPa)均显著高于对照组 (12 3mmHg± 17mmHg ,77mmHg±11mmHg) ,P <0 0 1;与对照组相比 ,病例组血清甘油三酯水平显著增高 (P <0 0 5 ) ,总胆固醇、低密度脂蛋白 胆固醇有增高趋势 ,但差异无显著意义 (P >0 0 5 )。 (2 )病例组ApoEE4 /3基因型 (2 4 0 % )和ε4等位基因型 (13 4 % )频率显著高于对照组 (12 9% ,7 2 % ) ;LDL RAvaⅡ位点 3种基因型和 2种等位基因型频率分布两组间差异无显著意义 ,但病例组携带ε4等位基因者同时携带AvaⅡ 位点的比例 (6 0 % )显著高于对照组 (31 8% ) ,P <0 0 5。 (3)调整年龄、性别、血压、体重指数后 ,两基因与烟、酒对冠心病发生的交互作用有显著意义的OR

Interaction of ApoE and LDL-R gene polymorphisms and alcohol drinking and smoking on coronary heart disease

OBJECTIVE: To investigate the association between the ApoE and LDLR-R gene loci on coronary heart disease (CHD) and their interaction with alcohol drinking and smoking in Hans of Chinese. METHODS: A questionnaire survey of the behaviors of smoking and drinking, dietary custom, and anamnesis, was conducted among 146 cases of CHD, aged 64 +/- 11, and 340 controls, aged 63 +/- 12. Peripheral blood samples were collected and the total DNAs were extracted. The levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were examined. The ApoE genotype was identified by the method of multiplex amplification refractory mutation system and AvaII polymorphisms of the LDL-R gene were detected by using the method of polymerase chain reaction-restriction fragment length polymorphism. The interaction between the genes and alcohol drinking and smoking was analyzed by using multivariate logistic regression models. RESULTS: (1) Both the systolic blood pressure and diastolic blood pressure of the CHD patients (132 mm Hg +/- 21 mm Hg, and 81 mm Hg +/- 13 mm Hg, 1 mm Hg = 0.133 kPa) were significantly higher than those of the controls (123 mm Hg +/- 17 mm Hg and 77 mm Hg +/- 11 mm Hg, both P < 0.05). The level of TG was 1.6 +/- 0.9 mmol/L in the CHD group, significantly higher than that in the control group (1.4 +/- 0.8 mmol/L, P < 0.05). However, there was no difference in the levels of TC, LDL-C, and HDL-C between the 2 groups (all P > 0.05). (2) For the ApoE gene, the frequencies of E4/3 genotype and epsilon 4 allele were 24.0% and 13.4% respectively in the CHD group, both significantly higher than those in the control group (12.9% and 7.2% respectively, both P < 0.05). For the LDLR-AvaII locus, no difference was found in different genotypes between the CHD and control groups. However, the proportion of those with epsilon 4 locus and AvaII(+) locus simultaneously was 60% in the CHD group, significantly higher than in the control group (31.8%, P < 0.05). (3) After adjustment of confounding variables, such as age, sex, blood pressure, and body mass index, the binary logistic analysis showed a significant gene-environment interaction (P < 0.05). The OR value were: for epsilon 4-AvaII(+): 2.99 (95% CI: 1.36 approximately 6.66, P < 0.01), for epsilon 3-often drinking: 2.60 (95% CI: 1.35 approximately 5.02, P < 0.01), for epsilon 3-smoking 2.58 (95% CI: 1.16 approximately 5.71, P < 0.05), for epsilon 4-stopped smoking 3.12 (95% CI: 1.23 approximately 8.09, P < 0.05), for epsilon 4-smoking: 5.30 (95% CI: 1.21 approximately 23.22, P < 0.05), and for AvaII(+)-often drinking: 2.49 (95% CI: 1.12 approximately 5.52, P < 0.05) respectively. CONCLUSION: The carriers of epsilon 3, epsilon 4 or AvaII(+) alleles would have higher risk of suffering from CHD if they are drink alcohol or smoke heavily.