title: Combined effects of apoE-CI-CII cluster and LDL-R gene polymorphisms on chromosome 19 and coronary artery disease risk.
abstract: OBJECTIVE
  To investigate associations of gene polymorphisms of the apoE-CI-CII gene cluster and the LDL-R gene on coronary artery disease (CAD) and their interactions with alcohol drinking and smoking in the Chinese Han population.
  
  
  METHODS
  A questionnaire survey of the behaviors of smoking and drinking, dietary patterns and anamnesis was conducted among 203 patients of CAD, aged 65.0 +/- 11.1 years, and 365 controls, aged 63.6 +/- 12.0 years. Peripheral blood samples were colleted and the total DNA was extracted. The apoE genotypes were identified by multiplex amplification refractory mutation system (multi-AMRS), the apoCI promoter polymorphisms and AvaII polymorphisms of the apoCII and LDL-R gene were detected by using PCR-RFLP. Pairwise linkage disequilibrium coefficients (D, D') were estimated by the LINKAGE program. The interactions between genes with alcohol drinking and smoking were analyzed by using multivariate logistic regression models.
  
  
  RESULTS
  The differences of systolic/diastolic blood pressure, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) concentrations, smoking and drinking were significant between subjects with CAD and controls. The frequencies of apoE gene epsilon 3/4 genotype (25.9%) and epsilon 4 (13.9%) in CAD were significantly higher than those in controls (12.5% and 6.9%, respectively, p < 0.05). A significant difference was also found for the apoCI locus, the frequencies of H2 allele were 20.5% in the CAD and 11.3% in the control. Linkage disequilibrium coefficient D' was 0.672 (p < 0.01) between apoE and apoCI genes. Significant differences for a deficit of epsilon 3-H1-T1 and excess of epsilon 4-H2-T1 was found in CAD by estimation of the haplotype frequencies. After control for possible confounding factors, the multivariate logistic analysis showed that epsilon 4, H2 allele, smoking and drinking were risk factors of CAD. A significant interaction among epsilon 4, H2 and smoking was observed (OR 18.3, 95% CI: 2.35-150.81, p < 0.05), it was a multiplicative model. An additive model was shown among epsilon 4, H2 and drinking (OR12.7, 95% CI: 2.8-58.6, p < 0.05).
  
  
  CONCLUSIONS
  The results suggested that both apoE and apoCI on chromosome 19 were the susceptibility locus for CAD, their linkage disequilibrium should be responsible for the development of CAD. Drinking and smoking enhance the genetic predisposition to CAD.
authors.affiliation: Department of Hygiene, School of Medicine, Wuhan University, DongHu Road 115, Wuhan 430071, PR China. chwang027@yahoo.com
authors.forename: Chunhong
authors.initials: C
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.forename: Shuiqing
authors.initials: S
authors.lastname: Ye
authors.forename: Dingfen
authors.initials: D
authors.lastname: Han
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Tan
authors.forename: Fang
authors.initials: F
authors.lastname: Zheng
authors.forename: Qun
authors.initials: Q
authors.lastname: Shi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking / Q000009:adverse effects / Q000453:epidemiology; D053302:Apolipoprotein C-I; D053304:Apolipoprotein C-II; D001056:Apolipoproteins C / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D002784:Cholesterol / Q000097:blood; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D003327:Coronary Disease / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D005810:Multigene Family / Q000235:genetics*; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D012306:Risk; D012907:Smoking / Q000009:adverse effects / Q000453:epidemiology; D014280:Triglycerides / Q000097:blood
chemical_list: D053302:Apolipoprotein C-I; D053304:Apolipoprotein C-II; D001056:Apolipoproteins C; D001057:Apolipoproteins E; D026502:LDL-Receptor Related Proteins; D014280:Triglycerides; D002784:Cholesterol