Five frequent polymorphisms of the PAI-1 gene - Lack of association between genotypes, PAI activity, and triglyceride levels in a healthy population

被引:98
作者
Henry, M
Chomiki, N
Scarabin, PY
Alessi, MC
Peiretti, F
Arveiler, D
Ferrieres, J
Evans, A
Amouyel, P
Poirier, O
Cambien, F
JuhanVague, I
机构
[1] CHU TIMONE,HEMATOL LAB,CJF INSERM 9312,F-13385 MARSEILLE 5,FRANCE
[2] INSERM,U258,PARIS,FRANCE
[3] MONICA PROJECTS,STRASBOURG,FRANCE
[4] MONICA PROJECTS,TOULOUSE,FRANCE
[5] MONICA PROJECTS,BELFAST,ANTRIM,NORTH IRELAND
[6] MONICA PROJECTS,LILLE,FRANCE
[7] INSERM,SC7,PARIS,FRANCE
关键词
PAI-1; PCR-SSCP; polymorphism; healthy subjects; PAI activity; metabolic parameters;
D O I
10.1161/01.ATV.17.5.851
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The main function of plasminogen activator inhibitor type 1 (PAI-1) is to decrease fibrinolysis, which leads to fibrin accumulation. An elevated plasma PAI-1 concentration has been identified as a risk factor for the development of myocardial infarction, and an association between 1 polymorphism of the PAI-1 promoter and plasma PAI-1 levels has been described. Our aim was to identify new polymorphisms in the PAI-1 gene and to further examine the relationship between PAI-1 genotypes and circulating PAI-1 levels. We report the presence of 4 new polymorphisms that were identified by nonisotopic single-strand conformational polymorphism analysis followed by sequencing. These polymorphisms were investigated in relation to PAI-1 levels in a sample of 256 healthy men, aged 50-59 years, from France and Northern Ireland. Two G/A substitutions were detected at positions -844 and +9785. The former is in strong positive linkage disequilibrium with the previously described 4G/5G polymorphism at position -675. Two polymorphisms in the 3' untranslated region were identified. One corresponds to a T/G substitution at position +11 053 and is in negative linkage disequilibrium with the G/A substitution (+9785). The other is a 9-nucleotide insertion/deletion located between nucleotides +11 320 and +11 345 in a threefold-repeated sequence. This polymorphism is in strong positive linkage disequilibrium with the G/A substitution (+9785). The overall heterozygosity provided by the 5 PAI-1 polymorphisms (including the 4 new variants and the 4G/5G polymorphism) was .77. No significant association was found between PAI activity and genotypes; furthermore, the well known associations between PAI activity and body mass index, serum triglycerides, or insulin were homogeneous according to PAI-1 genotypes.
引用
收藏
页码:851 / 858
页数:8
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