Association Of GPX1Gene Pro200Leu Polymorphism With Coronary Artery Disease

BackgroundHuman’s spectrum of disease has changed in recent years. In nowadays, cardiovascular diseases have become the leading cause of death of humanbeings. As an important component of cardiovascular diseases, coronary artery disease(CAD) has drawn more and more attention for its high incidence. Because most cases have pessimistic prognosis, CAD could do great harm to our health and affect our quality of life. At present, CAD has been the main cause of death and burden of disease worldwidely. Accordingly, it’s of great importance for us to investigate the mechanism and relevant risk factors of CAD.In nowadays, people have reached a agreement that the prevalence of CAD is affected by gene and environmental factors and several environmental factors could influence the heredity susceptibility of CAD. Reasonable quantity of studies have confirmed that oxidative stress (OS) caused by reactive oxygen species (ROS) and unbalance of antioxidant defense system lead to endothelial dysfunction which accelerates the progression of atherosclerosis. Glutathione peroxidasel (GPX1), an important component of internal defense system, distributes widely in our organizations. The C to T nucleotide mutation (rs1050450) at codon200of GPX1 gene leads to the amino acid substitution of Leucine (Leu) for Proline (Pro)(Pro200Leu).Evidence has been presented that the GPX1gene Pro200Leu polymorphism is associated with CAD, yet the results are controversial. Furthermore, researches exploring the effect of this mutation on premature CAD are scarce. So we performed a case-control study to detect if there was any relationship between GPX1gene Pro200Leu polymorphism and CAD, and assess the interactions between this mutation and other risk factors on premature CAD.Objectives1. To detect the association between GPX1gene Pro200Leu polymorphism and CAD;2. To evaluate the interaction between GPX1gene Pro200Leu polymorphism and smoking on premature CAD.MethodsA Hospital-based1:1non-matched case-control study was adopted in this research.Cases sre consist of894newly-diagnosed CAD patients in department of cardiology, Qilu Hospitan, Shandong University while334healthy persons who came to the Physical Examination Center for a medical checkup were selected as the controls. In order to detect the relationship between GPX1gene Pro200Leu polymorphism and CAD in different age groups, we divided the patients into two groups:the375premature CAD group diagnosed at or before age55for male and65for female and the other519late-onset CAD. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was utilized to detect the GPX1gene Pro200Leu polymorphism. Univariate and multivariate logistic regression models were performed to explore the effect of GPX1gene Pro200Leu polymorphism on CAD. Additive model of interaction analysis was applied to assess the interactions between GPXl gene Pro200Leu polymorphism and other risk factors on premature CAD.Results1. The relationship between GPX1gene Pro200Leu polymorphism and coronary artery diseaseThe allele and genotype distributions of GPX1gene Pro200Leu polymorphism were significantly different among the premature CAD group, late-onset CAD group and controls (P<0.05). Univariate and multivariate logistic regression analysis indicated that Pro200Leu polymorphism might serve as a risk factor of CAD.2. The effect on premature CAD of GPX1gene Pro200Leu polymorphism multiplied with other risk factorsPositive additive model interaction was discovered between GPX1gene Pro200Leu polymorphism and smoke on premature CAD, and GPX1gene Pro200Leu polymorphism can increase the risk of suffering from premature CAD among smokers.Conclusions1. The GPX1gene Pro200Leu polymorphism could increase the risk of CAD.2. There exists positive additive model interaction between GPX1gene Pro200Leu polymorphism and smoke on premature CAD.