Correlation Between TIM-4 Gene Polymorphism And CHD

BackgroundCoronary Atherosclerotic Heart Disease(CHD)is a complex disease caused by the long-term interaction between multiple genes and environmental factors,and it seriously threatens human health.In western developed countries,the annual death rate accounts for about 1/3 of the total mortality.In China,the incidence and death rate of CHD is increased rapidly in the past 30 years,accounting for 50%to 75%of the deaths from heart disease.CHD is a chronic inflammatory disease and monocyte-macrophage system plays a complex and decisive role in the formation of atherosclerotic plaques.In addition,the presence of lymphocytes in the lesions suggests that inflammation and immune responses play an important role in the development of atherosclerosis.In addition,coronary heart disease shows obvious familial accumulation and belongs to a genetic disease.A series of genes or mutations associated with CHD have been discovered worldwide through genome-wide association studies.Up to 2017,More than 60 susceptible genes have been found,out of which includes CXCL12,CCDC92,IL-6,MPO,TNF-? and other immune-related genes.The Tim gene family was discovered by McIntire in 2001 when they studied asthma susceptibility genes.Tim family affects the differentiation of T cells and is associated with a variety of immune diseases,such as diabetes,asthma and so on.The human Tim family includes three members:TIM-1,TIM-3 and TIM-4.TIM-4 is the natural ligand of TIM-1.TIM-1 and TIM-3 are mainly expressed on Th cells,while TIM-4 is mainly expressed on the surface of macrophages and dendritic cells.Recent research shows that the TIM-4 acts as a receptor for phosphatidylserine and promotes phagocytosis of apoptotic cells by binding to phosphatidylserine on the surface of apoptotic cells.TIM-4 can not only regulate the proliferation and activation of T cells,but also enhance the ability of phagocytes to engulf apoptotic cells.Therefore,TIM-4 plays a critical role in maintaining body homeostasis.Though association of TIM-4 gene polymorphisms with rheumatoid arthritis,asthma and SLE has been reported.However,the relationship between TIM-4 gene polymorphisms and coronary heart disease remains unclear at present,which needed further investigation.AimTo explore the correlation of the CHD with TIM-4 gene SNP and sTIM-4 in serum.To clarify the relationship between TIM-4 and susceptibility and severity of CHD,which would provide a new target for the diagnosis and prognosis of CHD.MethodCollect peripheral blood samples of CHD patients and healthy control.Collect blood and serum of CHD patients and healthy control group,and analyze the age,sex,smoking,drinking,serum lipid level and other related data.1.Extract peripheral blood genomic DNA by TIANGEN whole-blood genomic DNA extraction kit.2.Specific primers were designed according to rs 7700944 and rs 6882076 polymorphisms,and genotyping was performed using real-time quantitative PCR method to calculate genotype and allele frequency.3.Detect the level of sTIM-4 in the serum of healthy control group and CHD patients by enzyme-linked immunosorbent assay(ELISA).4.Compare the difference in genotype and allele frequencies of rs 7700944 and rs 6882076 between healthy control group and CHD.The differences of serum sTIM-4 levels in CHD and healthy controls were analyzed,and the differences of serum sTIM-4 levels in CHD patients with different genotypes at rs 7700944 were also assayed.The relationship between rs 7700944 genotypes and hypertension,diabetes,blood lipids and coronary scores in CHD were further analyzed.Results1.Compared with the healthy control group,patients with CHD have relatively high age,high proportion of men,and high proportion of smoking and drinking.In the blood lipid metabolism,patients with CHD show higher triglycerides(TG),lower HDL-C,but no statistical difference is found for low-density lipoprotein cholesterol(LDL-C)and total cholesterol(TC).2.There were no significant differences between rs 6882076 locus genotype and allele frequencies.TIM-4 gene rs 7700944 locus genotype and allele frequency distribution have a correlation with CHD,and rs 7700944 AA homozygous genotype is less susceptible to CHD.3.Compared with the healthy control group,patients with CHD have the lower concentration of sTIM-4 in serum.Compared with other genotypes,the serum sTIM-4 level in rs 7700944 AA homozygous genotype was significantly elevated.4.There were no differences in TC,TG,HDL-C,LDL-C for CHD patients with different genotypes at rs 7700944,but the Gensini score of CHD patients with AA genotype was higher than those with GG type.5.Serum sTIM-4 level was positively correlated with TG in CHD patients.No correlation between serum sTIM-4 level and other serum lipid and Gensini score was found.No correlation of sTIM-4 and Gensini score was either found in CHD patients with AA genotype at rs 7700944.In addition,individuals with different genotypes at rs 7700944 showed similar sensitive to attack diabetes or hypertension in CHD patients.Conclusion:1.sTIM-4 levels in CHD patients are lower than healthy controls,which indicates that sTIM-4 might prevent the development of CHD.2.TIM-4 gene rs 6882076 is not associated with CHD,while rs 7700944 is significantly correlated with CHD and AA genotype is less sensitive to CHD.3.CHD patients with rs 7700944 AA show higher sTIM-4 levels than those with other genotypes,but the coronary score of CHD patients with AA genotype was higher than those with GG type.In addition,serum sTIM-4 level was positively correlated with TG in CHD patients.