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심근경색의 위험인자로서 Thrombomodulin 유전자변이의 의의

DC FieldValueLanguage
dc.contributor.author지선하-
dc.date.accessioned2019-11-11T06:59:16Z-
dc.date.available2019-11-11T06:59:16Z-
dc.date.issued2000-
dc.identifier.issn1738-5520-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/172452-
dc.description.abstractThrombomodulin (TM) is thrombin receptor present on the luminal surface of endothelial cells. Because the thrombin-TM complex acts as an anticoagulant, the functional variants or deficiency of TM may lead to increment of thrombotic tendency. In this study, we screened the genetic variants of the TM gene in patients with myocardial infarction (MI) and analyzed the genotype to elucidate the effects of genetic variations of TM gene on the development of the MI. We screened a promoter region and coding sequence of the TM gene using single strand conformation polymorphism-heteroduplex analysis and identified three common genetic variants: those were TM G-33A, TM Ala455Val, and TM C1922T. The genotype frequencies were investigated in the patients with MI (n=234) and control subjects (n=291) by the method of allele-specific oligomer hybridization. The frequencies of mutant genotypes (TM -33A, TM 455Val, and TM 1922T) were higher in patient group compared to the control subjects in males while there were no significant differences in females. In the multiple logistic regression analysis, TM 455Val and TM 1922T alleles were independent risk factors for MI (OR[95% CI: 1.799[1.125-2.878] p=0.014 and 5.624[1.019-31.025], p=0.048, respectively) in males. However, the genetic variations were not independent risk factors for MI in females. There were significant linkage disequilibriums among three genetic variants. These linkage disequilibriums explain the similar effects of three genetic variants on the development of MI. To investigate the effect of the TM G-33A mutation on TM promoter activity, the two TM promoter constructs (pTM-355 and pTM-125, bearing TM -33G or TM -33A) containing of firefly luciferase gene were transfected into HepG2, BAE, and CHO cells. The promoter activities were higher in the promoter constructs with TM -33G compared to the constructs with TM -33A in pTM-355. These results suggest the possibility of the positive predisposing effect of TM -33A allele on MI in males. The functional study for TM Ala455Val and TM C1922T should be followed to elucidate the genotype effects of these mutations on the development of MI. In this study, we identified three genetic variants of TM gene and showed the significant associations between genetic variants and MI in males. These results proposed that TM gene is an attractive candidate for genetic risk factor for MI in Koreans.-
dc.description.statementOfResponsibilityopen-
dc.languageKorean-
dc.publisher대한심장학회-
dc.relation.isPartOfKorean Circulation Journal (순환기)-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.subject.MESHAlleles-
dc.subject.MESHAnimals-
dc.subject.MESHCHO Cells-
dc.subject.MESHClinical Coding-
dc.subject.MESHCricetinae-
dc.subject.MESHEndothelial Cells-
dc.subject.MESHFemale-
dc.subject.MESHFireflies-
dc.subject.MESHGenetic Variation-
dc.subject.MESHGenotype-
dc.subject.MESHHumans-
dc.subject.MESHLinkage Disequilibrium-
dc.subject.MESHLogistic Models-
dc.subject.MESHLuciferases-
dc.subject.MESHMale-
dc.subject.MESHMyocardial Infarction*-
dc.subject.MESHPhenobarbital-
dc.subject.MESHPromoter Regions, Genetic-
dc.subject.MESHReceptors, Thrombin-
dc.subject.MESHRisk Factors*-
dc.subject.MESHThrombomodulin-
dc.title심근경색의 위험인자로서 Thrombomodulin 유전자변이의 의의-
dc.title.alternativeGenetic Variants of Thromobomodulin Gene as Risk Factors for Myocardial Infarction-
dc.typeArticle-
dc.contributor.collegeGraduate School of Public Health (보건대학원)-
dc.contributor.departmentGraduate School of Public Health (보건대학원)-
dc.contributor.googleauthor박현영-
dc.contributor.googleauthor김영미-
dc.contributor.googleauthor권혁문-
dc.contributor.googleauthor지선하-
dc.contributor.googleauthor조승연-
dc.contributor.googleauthor정남식-
dc.contributor.googleauthor심원흠-
dc.contributor.googleauthor장양수-
dc.identifier.doi10.4070/kcj.2000.30.6.702-
dc.contributor.localIdA03965-
dc.relation.journalcodeJ01953-
dc.identifier.eissn1738-5555-
dc.subject.keywordthrombomodulin-
dc.contributor.alternativeNameJee, Sun Ha-
dc.contributor.affiliatedAuthor지선하-
dc.citation.volume30-
dc.citation.number6-
dc.citation.startPage702-
dc.citation.endPage715-
dc.identifier.bibliographicCitationKorean Circulation Journal (순환기), Vol.30(6) : 702-715, 2000-
Appears in Collections:
4. Graduate School of Public Health (보건대학원) > Graduate School of Public Health (보건대학원) > 1. Journal Papers

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