한국인의 허혈성 뇌경색 발생과 플라스미노겐 활성 억제인자-1(PAI-1) 유전자 다형성과의 관계
The Association of the -675 4G/5G and A-844G Polymorphisms of the Plasminogen Activator Inhibitor-1 Gene with a Risk of Ischemic Stroke in Korean Population
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
연구배경 : 플라스미노겐 활성 억제인자-1 (plasminogen activator inhibitor-1; PAI-1)은 허혈성 뇌경색의 발생의 원인이 되는 섬유소 용해작용의 저하를 매개하는 인자로서, PAI-1의 작용이 촉진되면 섬유소 용해기능이 저하되어 관상동맥 및 뇌혈관질환의 발생을 증가시키게 된다. PAI-1 유전자의 촉진자(promotor) 영역에는 -675 4G/5G (4G/5G)와 A -844G (A/G)의 두 개의 유전자 다형성이 존재하며, 이는 PAI-1의 유전자 전사과정에 영향을 미쳐 혈청 PAI-1의 농도를 증가시키고 결과적으로 허혈성 뇌경색의 발생확률을 높이는 작용을 하게 된다. 연구방법 : 허혈성 뇌경색으로 진단 받은 167명의 환자와 173명의 건강인의 말초혈액에서 DNA를 분리한 후 PAI-1의 4G/5G와 A/G 유전자 다형성에 대한 연쇄중합반응 및 제한효소 절편길이 다형성 (polymerase chain reaction-restriction fragment length polymorphism; PCR-RFLP) 방법을 이용하여 허혈성 뇌경색 발생과 유전자 다형성과의 관계를 비교 분석하였다. 결과 : 허혈성 뇌경색 환자에서의 4G/4G의 유전자형의 빈도는 15.0%으로 정상 대조군의 33.5%에 비해 현저하게 낮게 나타났다 (P < 0.0001). 각각의 유전자형과 허혈성 뇌경색의 발생 위험도 (odd ratio ; OR)와의 관계를 분석했을 때 4G/4G 유전자형을 가질 경우 위험도는 0.35배로 현저하게 낮아졌으며, (P < 0.0001), 5G/5G 유전자형을 가질 경우 위험도는 4.49배로 현저하게 높아졌다 (P < 0.0001). 그러나, A/G 유전자 다형성과 허혈성 뇌경색의 발생과는 유의한 연관성을 발견하지 못하였다. 결론 : 이상의 결과로 볼 때 PAI-1 유전자의 4G/4G 유전자형은 허혈성 뇌경색의 발생 비율을 감소시키는 작용을 하는 것으로 여겨진다.
Abstract
Objective : The plasminogen activator inhibitor (PAI)-1 is the major regulator of the fibrinolysis system which plays a key role in the development of ischemic stroke. Two polymorphisms, -675 4G/5G (4G/5G) and A -844G (A/G), in the PAI-1 promoter are associated with altered PAI-1 transcription, suggesting that these polymorphisms may be candidate risk factors for ischemic stroke. Methods : We genotyped ischemic stroke patients (n = 167) and the healthy control subjects (n = 173) for 4G/5G and A/G PAI-1 polymorphism by polymerase chain reaction-restriction fragment length polymorphism methods. Results : The frequency of 4G/4G genotype in the patients with ischemic stroke was significantly lower than that in the healthy controls (15.0% vs 33.5%, P < 0.0001). Decreased risk of ischemic stroke was associated with the 4G/4G genotype (OR = 0.35, 95% CI 0.21-0.59, P < 0.0001) and increased risk of ischemic stroke with the 5G/5G genotype (OR = 4.49, 95% CI 2.60-7.73, P < 0.0001). There was no significant difference detected in the allelic and genotype distributions of the A/G polymorphism between ischemic stroke patients and the healthy controls. Conclusions :These findings indicate that the 4G/4G, but not A/A, genotype is associated with a lower risk of ischemic stroke.
참고문헌 (20)
- "Increased fibrin turnover and high PAI-1 activity as predictors of ischemic events in atherosclerotic patients. A case-control study. The PLAT Group. Arterioscler Thromb 1993;13:1412-7.", pp.1412~7 (1993)
- "Demonstration of a fast-acting inhibitor of plasminogen activators in human plasma", 64, pp.907~13 (1984)
- "cDNA cloning of human plasminogen activator-inhibitor from endothelial cells", pp.1673~80
- "Cloning and sequence of a cDNA coding for the human beta-migrating endothelial-cell-type plasminogen activator inhibitor", 83, pp.6776~80 (1986)
- "Associations of fibrinogen factor VII and PAI-1 with baseline findings among 10 500 male participants in a prospective study of myocardial infarction--the PRIME Study Prospective Epidemiological Study of Myocardial Infarction", 80, pp.749~756 (1998)
- "Five frequent polymorphisms of the PAI-1 gene lack of association between genotypes and triglyceride levels in a healthy population", 17, pp.851~858 (1997)
- "The PAI-1 gene locus 4G", 5G polymorphism is associated with a family history of coronary artery disease, 1998, pp.18, 152~156
- "The 4G4G genotype of the plasminogen activator inhibitor 4G", 5G gene polymorphism is associated with coronary atherosclerosis in patients at high risk for this disease, 1999, pp.82, 1121~1126
- "4G", 5G polymorphism of the plasminogen activator inhibitor-1 gene and insertion, pp.2001, 11[DOI]
- "The 4G", 4G genotype at nucleotide position -675 in the promotor region of the plasminogen activator inhibitor 1 gene is less frequent in young patients with minor stroke than in controls, 2000, pp.110, 469~471
- "Plasminogen activator inhibitor 4G polymorphism is associated with decreased risk of cerebrovascular mortality in older women", 101, pp.67~70 (2000)
- "The association of PAI-1 promoter 4G", 5G insertion, pp.2002, 9[DOI]
- "The Ets family of transcription factors", 211, pp.7~18 (1993)
- "The A -844G polymorphism in the PAI-1 gene is associated with a higher risk of venous thrombosis in factor V Leiden carriers", 20, pp.1387~1391 (2000)
- "Polymorphisms of angiotensin converting enzyme and plasminogen activator inhibitor-1 genes in diabetes and macroangiopathy", 54, pp.1659~1669 (1998)
- "Plasminogen activator inhibitor-1 4G", 5G promoter polymorphism and coagulation factor VII Arg353Gln polymorphism in Korean patients with coronary artery disease, 2000, pp.15, 146~152
- "A novel G", A and the 4G, pp.1996, 84[DOI]
- "The impact of the PAI-1 A G promoter polymorphism on the risk and extent of coronary heart disease", 88, pp.697~698 (2002)
- "Allele-specific increase in basal transcription of the plasminogen-activator inhibitor 1 gene is associated with myocardial infarction", 92, pp.1851~1855 (1995)
- "Human monocyte-derived macrophages induce collagen breakdown in fibrous caps of atherosclerotic plaques Potential role of matrix-degrading metalloproteinases and implications for plaque rupture", 92, pp.1565~1569 (1995)