Relationship Between Genetic Polymorphisms And Susceptibility To Coronary Heart Disease In Han Population In Inner Mongolia

Background:Coronary Artery Disease(CAD)is one of the most common disease that harming human health even human life.CAD has become the leading cause death nowadays.Coronary artery disease is caused by interaction of environment factors and genetic factors.Of all the risk factors,genetic factor play an important part in coronary artery disease occurrence and development.The relationship between SNPs and CAD susceptibility has become the hot spot of coronary artery disease genetic research nowadays.Further investigation of SNPs in genes of these important pathways will provide new clues for understanding CAD susceptibility,genetic molecular basis,and help us evaluate CAD risk and preventing disease incidence.Purpose:In this study,we chose key genes in lipid metabolism LIPC(rs1800588),LPL(rs320),APOC3(rs5128),CETP(rs5882),PON1(rs662),APOA5(rs662799)and APOB(rs693),genes in inflammation pathway CRP(rs1205),ADIPOQ(rs1501299),IL6(rs1800796),and genes in rennin-angiotensin system ACE(rs4340),AGTR1(rs5186),AGT(rs699),and study the relationship between polymorphism and CAD susceptibility.We also study how the interactions of genotype and gender,smoking,hypertension,type 2diabetes mellitus influence CAD susceptibility.According to the results of the existing literature,the distribution of SNP genotypes in different countries and regions is different,and SNP interacts with the environment.Inner Mongolia region has local characteristics of customs and eating habits,but the current study of SNP in the region and the relationship between coronary heart disease susceptibility is lack.To this end,this project focuses on two scientific issues:first,the relationship between SNP and coronary heart disease susceptibility in Inner Mongolia population;second,the interaction between SNP and environment in Inner Mongolia area and its impact on coronary heart disease susceptibility.The key genes of lipid metabolism,immune,inflammation of the renin-angiotensin system would be studied on the relationship between people and coronary heart disease in Mongolia area,and the interaction analysis of common environmental factors with gene polymorphisms.The study would provide theoretical basis for the prevention of coronary heart disease in the region.Results:1.This research was used the case control study method and the sampling method using interval sampling in the Department of Cardiology in our hospital from 2015 to 2016 in the first month of each quarter,in accordance with the inclusion criteria and data integrity of all hospitalized patients into the study.A total of 435 cases were Han nationality in Inner Mongolia area were selected,with more than three generation requirements in Inner Mongolia residential area.196 cases were selected of the same healthy people of Han nationality in Inner Mongolia as a control group.Both the experimental group and the control group were informed of the details and signed the written informed consent before they were selected.This study has been approved by the ethics committee of our hospital.1.Polymorphism of lipid metabolism gene polymorphism and CAD susceptibilityAfter adjustment for gender,smoking,diabetes and hypertension,rs662799 of APOA5 is associated with CAD risk.Minor allele G of rs662799 is the risk allele(p=0.03,or = 1.374,95%CI=1.032-1.83).rs5882 of CETP is associated with CAD risk.Minor allele G of rs5882 is the risk allele(p = 0.048,or = 1.281,95%CI= 1.002-1.638).After adjustment for gender,smoking,diabetes and hypertension,there is no association between rs5882 and CAD risk(P = 0.128,OR = 1.222,95%CI = 0.944-1.581).In male group,rs662799 of APOA5 is significantly associated with CAD risk,and minor allele G is the risk allele(P = 0.003,OR =1.8,95%CI = 1.215-2.668).In smoking group,rs1800588 of LIPC is significantly associated with CAD risk,and minor allele T is the risk allele(P = 0.035,OR = 1.603,95%CI = 1.035-2.482).In hypertension group,rs662799 of APOA5 is significantly associated with CAD risk,and minor allele G is the risk allele(P = 0.004,OR = 1.792,95%CI=1.199-2.679).In non-hypertension group,rs5882 of CETP is significantly associated with CAD risk,and minor allele G is the risk allele(P = 0.023,OR = 1.593,95%CI = 1.067-2.379).2.Polymorphism of Immune and inflammation gene polymorphism and CAD susceptibilityAfter adjustment for gender,smoking,diabetes and hypertension,there is no association between rs1205,rs1501299,rs1800796 and CAD risk.In diabetes group,rs1501299 of ADIPOQ is significantly associated with CAD risk,and minor allele A is the risk allele(P = 0.026,OR = 2.85,95%CI = 1.136-7.149).3.Polymorphism of rennin-angiotensin system gene polymorphism and CADsusceptibilityAfter adjustment for gender,smoking,diabetes and hypertension,there is no association between rs4340,rs5186,rs699and CAD risk.Conclution:This study focus on 13 SNPs in lipid metabolism,Immune and inflammation and rennin-angiotensin system genes,combining multiplex PCR and next generation sequencing technology,evaluate the relationship between SNP polymorphism and CAD susceptibility.1,rs662799 of APOA5 gene is associated with CAD susceptibility,and G allele carriers have higher risk of CAD occurance.2,In male group,rs662799 of APOA5 gene is associated with CAD susceptibility,and G allele carriers have higher risk of CAD occurance.3,In smoking group,rs1800588 of LIPC gene is associated with CAD susceptibility,and T allele carriers have higher risk of CAD occurance.4,In hypertension group,rs6.62799 of APOA5 gene is associated with CAD susceptibility,and G allele carriers have higher risk of CAD occurance.In non-hypertension group,rs5882 of CETP gene is associated with CAD susceptibility,and G allele carriers have higher risk of CAD occurance.5,In diabetes group,rs1501299 of ADIPOQ gene is associated with CAD susceptibility,and A allele carriers have higher risk of CAD occurance.6,.There is no association between LPL(rs320),APOC3(rs5128),PON 1(rs662),APOB(rs693),CRP(rs1205),IL6(rs1800796),ACE(rs4340),AGTR1(rs5186),AGT(rs699)gene polymorphism and risk of CAD occurance.The difference among SNP genotypes in Inner Mongolia area and the Han nationality maybe exist.The relationship between SNP and coronary heart disease may be different from the other countries and regions,and about the relations between the two is to expand the sample size and types of SNP for further study.