| BackgroundCoronary artery disease (CAD) is a multifactor disorder that is thought to result from an interaction between genetic background and environmental factors such as diet, smoking, and physical activity.In the human genome, between 20930 to 27160 genes are estimated to be expressed in the human cardiovascular system. Most research to date has focused on the individual effects of each single nucleotide polymorphisms (SNPs) on the specific pathway contributing to CAD.So, genetic epidemiological studies have suggested that certain genetic polymorphisms in apolipoprotein (Apo)E, ApoCI and ApoCII genes are associated with an increased prevalence of CAD. In human genome structure, the apoE gene lies at a cluster with the ApoCI and ApoCII at the long arm of chromosome 19 (19ql3.2). The Apo E-CI-CII cluster gene spans approximately 48kb. It was reported that genetic interaction between the ApoE and ApoCI gene could modify a risk factor of ApoE- ε 4 for Senile Dementia of Alzheimer's Type. Therefore, we could hypothesize that genetic interaction among the ApoE and ApoCI gene could influence the genetic contribution of Apo e 4 to CAD. The human low-density lipoprotein receptor (LDL-R) gene has also been mapped to chromosome 19pl3.2. This gene is approximately 45 kb long and contains 18 exons separated by 17 introns. The Avail polymorphisms in exon 13 and Ncol polymorphisms in exon 18 have been found to affect total cholesterol (TC) and LDL-C levels in the general population.One report suggested that smoking increased the risk of CAD in men of all apoE genotypes, particularly in men carrying the ApoE gene ?4 allele. It means that both gene and environmental factor can be affected by each other during the development and promotion of CAD. Thus, it is important to consider the associations of multiple genes and their interactions with environmental factors (such as smoking and alcohol consumption) in order to understand CAD.ObjectiveTo understand the effect of environmental factors on CAD in a Chinese Han population of Hubei province.To investigate association of gene polymorphisms of the ApoE-CI-CII gene cluster and LDL-R gene locus with CAD.To find that the interplay between the common behavioral factors (alcohol drinking and smoking) and genetic polymorphisms in this population as the effect modifier of risk factors to CAD.MethodsA questionnaire survey of the behaviors of smoking and drinking, dietary pattern, and anamnesis, was conducted among 203 (male 121, female 82 ) patients of CAD, aged 65.2?1.1( ranging 41-88 )years old and 365 (male204, female 161)controls, aged 63.6?12.0 ( ranging 40-87 )years old. The cases had been admitted for angiography for suspected CAD at Zhongnan Hospital, and controls were confirmed by anamnesis, physical examination, and investigation by electrocardiogram. Control individual who suffered from severe systemic disease which potentially influence the cardiovascular risk factor profile were excluded.Peripheral blood samples were colleted and the total DNAs were extracted. The ApoE genotypes were identified by multiplex amplification refractory mutation system (multi-AMRS), the ApoCI promoter polymorphisms and Avail polymorphisms of the ApoCII gene in 3 intron and LDL-R gene in 13 exon were detected by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The serum lipkl levels were determined using an automatic chemistry analyzer.Linkage disequilibrium between the ApoE and ApoCI was tested by estimation of haplotype frequencies performed by the EH program. The OR of susceptibility of the genes to CAD and the attributable proportions of interaction (API) of interactions with alcohol drinking and smoking were analyzed by using multivariate logistic regression models.ResultsThe differences of systolic/diastolic blood pressure, TG, LDL-C and ApoB concentrations, and ApoAl/B were significance between subjects with CAD and controls, P<0.05.From the stepwise logistic regression analyses: blood pressure, LDL-C level, smoking and...
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