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Association Of TREM-1 Gene Polymorphism And Serum STREM-1 With Susceptibility To Coronary Heart Disease

Posted on:2019-05-26Degree:MasterType:Thesis
Country:ChinaCandidate:J LuFull Text:PDF
GTID:2394330545464111Subject:Clinical Laboratory Science
Abstract/Summary:PDF Full Text Request
Coronary heart disease is a chronic disease,which is mainly due to the gradual narrowing of blood vessels supplying oxygen to myocardium.When the consumption of oxygen increased,there would be a phenomenon of insufficient blood supply,and clinical manifestations include stable angina pectoris(SAP)and acute coronary syndrome(ACS).The main pathological basis of coronary heart disease is atherosclerosis,a chronic inflammatory process of progressive thickening of the arterial wall.Currently,coronary heart disease is a common cardiovascular disease around the world and seriously threatens the human health,so it has become a healthy problem that humans keep eyes on.However,the effective treatment of coronary heart disease against the inflammation has not been found in clinical practice.Thus,further exploration of the pathological mechanism of coronary heart disease is very important for preventing and controlling the occurrence and development of coronary heart disease,improving the quality of life and prolonging the survival time.Triggering receptor expressed on myeloid cells-1(TREM-1),a kind of immunoglobulin superfamily activation receptor,is one of the members of the TREM family.The ways of TREM-1 being in vivo include membrane binding type(TREM-1)and soluble type(sTREM-1).Through coupling with the DNAX activator protein 12(DAP12),TREM-1could trigger the cascade reaction of downstream signal pathways,enhance the activity of nuclear factor-kappa B(NF-κB)and promote NF-κB P50/P65 subunit transportation to the nucleus,which would start up the expression of inflammatory factors and play an important role in atherosclerosis.Therefore,TREM-1 gene might be a susceptible gene for coronary heart disease.Objective:To investigate the association between TREM-1 gene polymorphism(rs2234237and rs9471535),serum sTREM-1 and coronary heart disease and analyze the effect of TREM-1 gene polymorphism(rs2234237 and rs9471535)on the expression of serum sTREM-1.Methods:Case-control study was used for study.120 patients with coronary heart disease were selected as the coronary heart disease group.According to the Foundation of the American College of Cardiology/American Heart Association(ACCF/AHA),coronary heart disease group was divided into two subgroups(subtypes),including 17patients with SAP and 103 patients with ACS.90 healthy people were selected as the control group at the same time.The single nucleotide polymorphisms(SNPs)of TREM-1gene(rs2234237 and rs9471535)were analyzed using Sanger method in all subjects.The level of serum sTREM-1 were analyzed using enzyme-linked immunosorbent assay(ELISA).SPSS23.0 statistical software was used to analyze data.Comparing baseline clinical data and the distribution of genotypes and alleles frequencies in groups.Non conditional logistic regression was used to analyze the relationship between TREM-1 gene(rs2234237 and rs9471535)polymorphisms and susceptibility to coronary heart disease and its subtype.Correlation analysis was used to analyze the relevance between TREM-1 gene(rs2234237 and rs9471535)polymorphisms and the severity of coronary heart disease as well as between serum sTREM-1 and the severity of coronary heart disease.Comparing serum sTREM-1 level among genotypes of rs2234237 as well as among genotypes of rs9471535 respectively to analyse the effect of TREM-1 gene(rs2234237 and rs9471535)polymorphisms on the expression of serum sTREM-1.Results:1.The proportion of smoking,hypertension,diabetes and dyslipidemia as well as the level of fasting plasma glucose(FBG)in the coronary heart disease group were significantly higher than the control group(P<0.05),while HDL-C level was significantly lower than the control group(P<0.05).In the subgroup of coronary heart disease,the proportion of hypertension and the level of age in SAP group were significantly higher than the control group(P<0.05).In the subgroup of coronary heart disease,the proportion of smoking,hypertension,diabetes and dyslipidemia as well as the level of FBG and triglyceride(TG)in ACS group were significantly higher than the control group(P<0.05),while HDL-C level was significantly lower than the control group(P<0.05).In addition,compared with SAP group,the proportion of dyslipidemia as well as the level of TG in ACS group significantly increased(P<0.05),while HDL-C level significantly reduced(P<0.05).The distribution of rs2234237,rs9471535genotypes was statistically significant between the coronary heart disease group and the control group(χ~2=6.893,P<0.05;χ~2=8.284,P<0.05,respectively).The A allele frequency of rs2234237 in the coronary heart disease group was significantly higher than in the control group,while the T allele frequency of rs2234237 was significantly lower than in the control group(all P<0.05).The A allele frequency of rs9471535 in the coronary heart disease group was significantly higher than in the control group,while the G allele frequency of rs9471535 was significantly lower than in the control group(all P<0.05).The distribution of rs2234237,rs9471535 genotypes was not statistically significant between SAP group and the control group(all P>0.05).Similarly,the alleles frequencies of rs2234237,rs9471535 was not statistically significant between SAP group and the control group(all P>0.05).The distribution of rs2234237,rs9471535 genotypes was statistically significant between ACS group and the control group(χ~2=11.262,P<0.05;χ~2=11.668,P<0.05,respectively).The A allele frequency of rs2234237 in ACS group was significantly higher than in the control group,while the T allele frequency of rs2234237 was significantly lower than in the control group(all P<0.05).The A allele frequency of rs9471535 in ACS group was significantly higher than in the control group,while the G allele frequency of rs9471535 was significantly lower than in the control group(all P<0.05).The distribution of rs2234237,rs9471535 genotypes was statistically significant between ACS group and SAP group(χ~2=9.808,P<0.05;χ~2=6.584,P<0.05,respectively).The A allele frequency of rs2234237 in ACS group was significantly higher than SAP group,while the T allele frequency of rs2234237 was significantly lower than in SAP group(all P<0.05).Similarly,the A allele frequency of rs9471535 in ACS group was higher than SAP group,while the G allele frequency of rs9471535 was lower than SAP group,but the difference was not statistically significant(all P>0.05).Through non conditional logistic regression analysis,all genetic models of rs2234237 were not related to susceptibility to coronary heart disease(all P>0.05).The recessive model and additive model of rs9471535 were related to susceptibility to coronaryheartdisease(OR=0.196,95%CI:0.050~0.768,P<0.05;OR=0.197,95%CI:0.050~0.785,P<0.05,respectively),while the dominant model and overdominant model were not related to susceptibility to coronary heart disease(all P>0.05).All genetic models of rs2234237 were not related to susceptibility to SAP(all P>0.05).Similarly,all genetic models of rs9471535 were not related to susceptibility to SAP(all P>0.05).The recessive model and additive model of rs2234237 were related to susceptibility to ACS(OR=0.058,95%CI:0.008~0.429,P<0.05;OR=0.061,95%CI:0.008~0.456,P<0.05),while the dominant model and overdominant model were not related to susceptibility to ACS(all P>0.05).Similarly,the recessive model and additive model of rs9471535 were related to susceptibility to ACS(OR=0.045,95%CI:0.006~0.327,P<0.05;OR=0.047,95%CI:0.006~0.344,P<0.05),while the dominant model and overdominant model were not related to susceptibility to ACS(all P>0.05).2.There was no correlation between the polymorphisms of rs2234237,rs9471535and the number of the coronary artery disease(all P>0.05).There was no correlation between the polymorphisms of rs2234237,rs9471535 and the degree of coronary stenosis(all P>0.05).3.Compared with the control group,the level of serum sTREM-1 in coronary heart disease group was significantly higher(P<0.05).In the subgroup of coronary heart disease,the level of serum sTREM-1 in SAP group was significantly lower than in the control group(P<0.05),while the level of serum sTREM-1 in ACS group was significantly higher than in the control group(P<0.05).Compared with SAP group,the level of serum sTREM-1 in ACS group was significantly higher(P<0.05).Serum sTREM-1 level was positively related to the number of coronary artery disease(r=0.238,P<0.05).Itwasalsopositivelyrelatedtothedegreeofcoronary stenosis(r=0.365,P<0.05).4.The difference of serum sTREM-1 level among genotypes of rs2234237 or rs9471535 was not statistically significant(all P>0.05).Conclusion:1.The TREM-1 rs2234237 polymorphism is closely related to the susceptibility to ACS subtype of coronary heart disease,the TT genotype might be a protective factor for ACS.The TREM-1 rs9471535 polymorphism is related to the susceptibility to coronary heart disease,especially closely related to the susceptibility to ACS,the GG genotype might be a protective factor for coronary heart disease(especially ACS).2.The polymorphisms of TREM-1 gene(rs2234237and rs9471535)were not related to the number of coronary artery disease or the degree of coronary stenosis.That is to say,the polymorphisms of TREM-1 gene(rs2234237 and rs9471535)were not related to the severity of coronary heart disease.3.The level of serum sTREM-1 was higher in ACS patients,and it was positively related to the number of coronary artery disease and the degree of coronary stenosis.That is to say,the level of serum sTREM-1 was related to the severity of coronary heart disease.4.The difference of serum sTREM-1 level among genotypes of rs2234237 or rs9471535 was not statistically significant.That is to say,the polymorphisms of TREM-1 gene(rs2234237 and rs9471535)might have no effect on the expression of serum sTREM-1.
Keywords/Search Tags:triggering receptor expressed on myeloid cells-1, single nucleotide polymorphism, soluble triggering receptor expressed on myeloid cells-1, coronary heart disease
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