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.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.(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). (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.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.