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

Research Unit of Hematological and Autoimmune Diseases, Faculty of Pharmacy, University of Monastir, Monastir, Tunisia.
Genetic Testing and Molecular Biomarkers (Impact Factor: 1.46). 11/2009; 14(1):23-7. DOI: 10.1089/gtmb.2009.0039
Source: PubMed


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.
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.
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.
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.
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.

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    • "In 2009, Isordia-Salas I et al. found that the 4G allele is an independent risk factor for acute MI in young patients, similar to smoking, hypertension, and a family history of inherited cardiovascular disease in Mexico [5]. In 2010, Abboud N et al. found that the MI risk is notably high in 4 G carriers with elevated plasma PAI-1 in a Tunisian population [6]. However, in 2011, Rallidis LS et al. found that the 4 G allele of PAI-1 4G/5G polymorphism is less frequent among very young survivors of MI compared with that in matched controls in Greece [7]. "
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