Morange, PE; Saut, N; Alessi, MC; Yudkin, JS; Margaglione, M; Di Minno, G; ... Juhan-Vague, I; + view all Morange, PE; Saut, N; Alessi, MC; Yudkin, JS; Margaglione, M; Di Minno, G; Hamsten, A; Humphries, SE; Tregouet, DA; Juhan-Vague, I; - view fewer (2007) Association of plasminogen activator inhibitor (PAI)-1 (SERPINE1) SNPs with myocardial infarction, plasma PAI-1, and metabolic parameters - The HIFMECH study. ARTERIOSCL THROM VAS , 27 (10) 2250 - 2257. 10.1161/ATVBAHA.107.149468.
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Objective-The purpose of this study was to investigate the effects of plasminogen activator inhibitor-1 (PAI-1) gene (SERPINE1) single nucleotide polymorphisms ( SNPs) on the risk of myocardial infarction (MI), on PAI-1 levels, and factors related to the metabolic syndrome.Methods and Results-Eleven SNPs capturing the common genetic variation of the SERPINE1 gene were genotyped in the HIFMECH study. In the 510 male cases and their 543 age-matched controls, a significant gene-smoking interaction was observed. In nonsmokers, the rs7242-G allele was more frequent in cases than in controls (0.486 versus 0.382, P=0.013) whereas the haplotype derived from the rs2227631 (-844A > G)-G and rs2227683-A alleles was approximate to 3-fold lower in cases than in controls (0.042 versus 0.115, P=0.006). SERPINE1 haplotypes explained 3.5% (P=0.007) of the variability of PAI-1 levels, which was attributable to the combined effects of 3 SNPs, -844A > G, rs2227666, and rs2227694. The rs6092 (Ala15Thr) and rs7242 SNPs acted additively to explain 4.4% of the variability of plasma insulin levels and 1.6% of the variability of BMI (P < 10(-3) and P=0.023, respectively).Conclusions-SERPINE1 haplotypes are mildly associated with plasma levels of PAI-1 and with the risk of MI in nonsmokers. They are also associated with insulin levels and BMI.
|Title:||Association of plasminogen activator inhibitor (PAI)-1 (SERPINE1) SNPs with myocardial infarction, plasma PAI-1, and metabolic parameters - The HIFMECH study|
|Keywords:||metabolic syndrome, myocardial infarction, PAI-1, SERPINE1, CORONARY-HEART-DISEASE, DEPENDENT DIABETES-MELLITUS, INSULIN-RESISTANCE SYNDROME, GENE POLYMORPHISMS, 4G/5G POLYMORPHISM, HEMOSTATIC MARKERS, ARTERY-DISEASE, RISK-FACTOR, PROMOTER, TYPE-1|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science|
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