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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    ABSTRACT: The polymorphism of plasminogen activator inhibitor-1 (PAI-1) 4G/5G gene has been indicated to be correlated with coronary artery disease (CAD) susceptibility, but study results are still debatable. The present meta-analysis was performed to investigate the association between PAI-1 4G/5G gene polymorphism and CAD in the Chinese Han population. A total of 879 CAD patients and 628 controls from eight separate studies were involved. The pooled odds ratio (OR) for the distribution of the 4G allele frequency of PAI-1 4G/5G gene and its corresponding 95% confidence interval (CI) was assessed by the random effect model. The distribution of the 4 G allele frequency was 0.61 for the CAD group and 0.51 for the control group. The association between PAI-1 4G/5G gene polymorphism and CAD in the Chinese Han population was significant under an allelic genetic model (OR = 1.70, 95% CI = 1.18 to 2.44, P = 0.004). The heterogeneity test was also significant (P<0.0001). Meta-regression was performed to explore the heterogeneity source. Among the confounding factors, the heterogeneity could be explained by the publication year (P = 0.017), study region (P = 0.014), control group sample size (P = 0.011), total sample size (P = 0.011), and ratio of the case to the control group sample size (RR) (P = 0.019). In a stratified analysis by the total sample size, significantly increased risk was only detected in subgroup 2 under an allelic genetic model (OR = 1.93, 95% CI = 1.09 to 3.35, P = 0.02). In the Chinese Han population, PAI-1 4G/5G gene polymorphism was implied to be associated with increased CAD risk. Carriers of the 4G allele of the PAI-1 4G/5G gene might predispose to CAD.
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    ABSTRACT: The allele and genotype frequencies of 14 SNPs of renin-angiotensin (REN, AGT, AGTR1, AGTR2, BKR2, and ADRB2) and hemostasis (FGB, F2, F5, F7, ITGB3, SERPINE1, MTHFR) system genes, as well as of the ACE insertion-deletion polymorphism, were analyzed in patients with ischemic stroke and in healthy controls matched by age, sex, and ethnicity. Genotyping was performed through the amplification of the selected gene sequences and subsequent hybridization of the labeled fragments with SNP-specific DNA probes on the biochip. There were no significant differences in the allele frequencies of individual genes between the groups of stroke patients and healthy donors. The contribution of the renin-angiotensin and hemostasis system genes to the genetic susceptibility to ischemic stroke in Russians from central Russia was also assessed using the MDR (Multifactor Dimensionality Reduction) approach. The genotype combination FGB G/- x ACE I/- x MTHFR C/- x SERPINE1 5G/5G, the frequency of which was significantly higher in patients with stroke than in healthy controls, was associated with an increased risk of ischemic stroke (P = 0.03, OR = 2.4, 95%CI 1.1–5.3).
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