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 approximately 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.
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 approximately 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.
Authors: P Bogdanski; M Szulinska; J Suliburska; D Pupek-Musialik; A Jablecka; H Witmanowski Journal: J Endocrinol Invest Date: 2012-06-25 Impact factor: 4.256
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Authors: J A Schoenhard; F W Asselbergs; K A Poku; S A Stocki; S Gordon; D E Vaughan; N J Brown; J H Moore; Scott M Williams Journal: Hum Genet Date: 2008-10-25 Impact factor: 4.132