Association of plasminogen activator inhibitor (PAI)-1 (SERPINE1) SNPs with myocardial infarction, plasma PAI-1, and metabolic parameters: the HIFMECH study.
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.


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.
INSERM, U626, Université de la Méditerranée, Marseille, France. pmorange@ap-hm.fr
P E
PE
Morange
N
N
Saut
M C
MC
Alessi
J S
JS
Yudkin
M
M
Margaglione
G
G
Di Minno
A
A
Hamsten
S E
SE
Humphries
D A
DA
Tregouet
I
I
Juhan-Vague
D015992:Body Mass Index; D016022:Case-Control Studies; D005060:Europe; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007328:Insulin / Q000097:blood; D015810:Linkage Disequilibrium; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000150:complications* / Q000235:genetics / Q000503:physiopathology; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D010641:Phenotype; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000235:genetics; D044465:White People / Q000235:genetics
D007328:Insulin; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human