Association of plasminogen activator inhibitor (PAI)-1 (SERPINE1) SNPs with myocardial infarction, plasma PAI-1, and metabolic parameters: the HIFMECH study.
Arterioscler Thromb Vasc Biol
; 27(10): 2250-7, 2007 Oct.
Article
in En
| MEDLINE
| ID: mdl-17656673
ABSTRACT
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 ANDRESULTS:
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.
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Database:
MEDLINE
Main subject:
Plasminogen Activator Inhibitor 1
/
Polymorphism, Single Nucleotide
/
Metabolic Syndrome
/
Myocardial Infarction
Type of study:
Clinical_trials
/
Etiology_studies
/
Observational_studies
/
Risk_factors_studies
Limits:
Humans
/
Male
/
Middle aged
Country/Region as subject:
Europa
Language:
En
Year:
2007
Type:
Article