Association of PAI-1 4G/5G and -844G/A gene polymorphisms and changes in PAI-1/tissue plasminogen activator levels in myocardial infarction: a case-control study.
BACKGROUND
Myocardial infarction (MI) is induced by acquired and inherited risk factors, including the plasminogen activator inhibitor-1 (PAI-1) -844G/A and -675G/A (4G/5G) gene variants.


OBJECTIVE
The aim of this study was to investigate the association between PAI-1-844G/A and 4G/5G polymorphisms and changes in PAI-1 and tissue plasminogen activator (tPA) levels in MI in a Tunisian population.


METHODS
This was a case-control study involving 305 patients with MI and 328 unrelated healthy controls. PAI-1 genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (RFLP) (-844G/A) or by polymerase chain reaction-allele specific amplification. PAI-1 and tPA levels were assayed by serological assays.


RESULTS
In contrast to tPA levels, mean plasma PAI-1 antigen levels were higher in cases than in control subjects. The elevation in PAI-1 levels was more pronounced in -844A and 4G allele carriers. Significantly higher frequencies of (mutant) 4G and -844A alleles and 4G/4G and -844A/-844A genotypes, and corresponding lower frequencies of (wild-type) 5G and -844G alleles and 5G/5G and -844G/-844G genotypes were seen in patients than in controls. Increased prevalence of 4G/-844A and decreased prevalence of 5G/-844G haplotypes were seen in patients than in controls, thereby conferring a susceptibility and protective nature to these haplotypes, respectively. Regression analysis confirmed the independent association of 4G/4G and -844A/A with MI, after controlling for a number of covariates.


CONCLUSIONS
This study indicated that the risk of MI was notably high in 4G and -844A carriers with elevated plasma PAI-1 and were associated with reduced tPA levels.
Abboud
Nesrine
N
Research Unit of Hematological and Autoimmune Diseases, Faculty of Pharmacy, University of Monastir, Monastir, Tunisia.
Ghazouani
Lakhdar
L
Saidi
Sarra
S
Ben-Hadj-Khalifa
Sonia
S
Addad
Fawzi
F
Almawi
Wassim Y
WY
Mahjoub
Touhami
T
D000368:Aged; D000483:Alleles; D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000235:genetics*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood* / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D010959:Tissue Plasminogen Activator / Q000097:blood*; D014416:Tunisia
D017931:DNA Primers; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D010959:Tissue Plasminogen Activator