The Interaction Between Angiotensinogen Gene Polymorphism And Traditional Risk Factors Of Coronary Artery Disease

Coronary artery disease(CAD) is a main public health issue around the world, leading to serious consequences. The pathogenesis is thought to result from an interaction between genetic background and environmental factors, studies have shown that genetic factors play an important role in the occurrence and development of CAD. With the accomplishment of the Human Genome Project, disease-related gene polymorphism has become a major medical genetics contents. As the third generation of genetic markers, single nucleotide polymorphism(SNP) is characterized by large numbers and dispersed distribution. Through comparisons between case and control groups and statistical analysis of related SNP, especially coding region and regulatory region,may be find disease-related SNP or haplotype, it is of special significance for understanding the genetic mechanisms of certain complex diseases. Recent studies show that and CAD is closely related Angiotensinogen (AGT) gene M235T and T174M polymorsm. However, the results have been inconsistent.In the present study,we investigated whether or not the interaction between the polymorphism and CAD risk factors have the ability to cause disease.To date,there are still no relevant studies has been reported in our country.Objective:Genotyping of M235T and T174M use PCR methods in the part of the Han population.Calculating genotype frequencies,haplotype analysis and analyzing the significance of the interaction between the polymorphism and environmental factors use related software for CAD risk.Methods:63CAD patients and53healthy individuals confirmed by coronary angiography in the First Affiliated Hospital of Yangtze University. Using matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) technology to detect AGT gene M235T and T174M polymorphism; Using two classification of non-conditional logistic regression to analyse independent risk factors for CAD; SHEsis statistical software is used for haplotype analysis;Using additive interaction by use of the Four-by-two table to analyze the interaction between the AGT gene polymorphism and CAD risk factors.Results:For M235T, the main genotype of patients and controls were TT(76.2%VS.68.4%), the main allele of patients and controls were T(88.1%vs.84.2%); For T174M, the main genotype of patients and controls were TT(81.0%VS.68.4%), the main allele of patients and controls were T(85.7%vs.78.9%); Logistic regression analysis showed that M235T gene TT genotype carriers increased the CAD risk(OR=1.26,95%CI=1.03-1.52)5M235T and T174M polymorphisms were in linkage disequilibrium,The linkage disequilibrium coefficient D’=0.770, Haplotype Hap3(235T and174T) of AGT gene account for the highest proportion, The frequency was73.8%vs.68.8%. But haplotype did not increased the CAD risk; Both gene polymorphism and traditional CAD risk factors were included in our study using the Four-by-two table, the results showed that M235T gene TT genotype carriers with diabetes(SI=2.63) or hypertension(SI=1.03) synergistically increased the risk of CAD.Conclusions:Compared with other races, AGT gene polymorphisms of Chinese Han population has unique characteristics of distribution; haplotype did not increased the CAD risk; M235T gene TT genotype carriers with diabetes or hypertension synergistically increased the CAD risk. In this study, case-control study was used to analyze whether or not the interaction between the AGT gene polymorphism and traditional CAD risk factors cause the occurrence of CAD. The findings not only provide a reference basis for further similar studies,but also is significant to the determination of high-risk groups and prevention and treatment of CAD.