Plasminogen Activator Inhibitor-1 (PAI-1) gene 4G/5G alleles frequency distribution in the Lebanese population

Abstract

Plasminogen activator inhibitor-1 (PAI-1) is an inhibitor of fibrinolysis. Increased plasma PAI-1 levels play an essential role in the pathogenesis of cardiovascular risk and other diseases associated with thrombosis. The 4G/5G polymorphism of the PAI-1 promoter region has been extensively studied in different populations. We studied 160 healthy unrelated Lebanese individuals using a reverse hybridization PCR assay to detect the 5G/5G, 4G/5G and, 4G/4G genotypes of the PAI-1 gene and the frequencies of the 4G and 5G alleles. We found that 4G/5G genotype was the most prevalent (45.6%) followed by 5G/5G (36.9%) and 4G/4G (17.5%). The frequencies of the 4G and 5G alleles were calculated to be 0.403 and 0.597, respectively. Compared to other ethnic communities, the Lebanese population was found to harbour a relatively high prevalence of the rare 4G allele. This, in turn, may predispose this population to develop cardiovascular diseases and other thrombotic clinical conditions. This study aids to enhance our understanding of the genetic features of the Lebanese population.

High Incidence of ACE/PAI-1 in Association to a Spectrum of Other Polymorphic Cardiovascular Genes Involving PBMCs Proinflammatory Cytokines in Hypertensive Hypercholesterolemic Patients: Reversibility with a Combination of ACE Inhibitor and Statin

“…Wild-type PAI-1 (5G/5G) gene was present in the Healthy and the HH groups (21.1% vs. 10.4%, respectively) while the heterozygous genotype (4G/5G) was expressed in 60.2% and 73.6% of the population and the homozygous genotype (4G/4G) in 18.7% and 16.0%, respectively. Our results on the PAI-1 distribution were a bit different than those obtained by Shammaa et al [ 28 ] (45.6%, 36.9% and 17.5% for 4G/5G, 5G/5G and 4G/4G, respectively). The difference between our study and the other studies could be explained by the very wide heterogeneity of the Lebanese population [ 36 ] or by the selection of the studied populations.…”

“…Thus, it becomes increasingly more important to understand if they coexist or not. Although the prevalence of each risk factor has been studied individually [ 27 , 28 ], the prevalence of the double mutation alone or in association with other atheroscleroris or venous thrombosis related genes has never been investigated neither in healthy nor in hypertensive hypercholesterlomic (HH) patients. Thereby, we conducted a screening analysis of the polymorphisms of these two genes as well as other CVD related genes in 315 Lebanese unrelated individuals (171 controls and 144 hypertensive hypercholesterlemic patients) and analyzed the impact of the “Del” allele and/or “4G” allele in ACE and PAI-1, respectively, on the state (wild-type versus mutated) of all selected genes.…”

Significance of the use of the ViennaLab “Cardiovascular Disease panel” (CVD) Assay as a reflex test for the “Factor V/II/MTHFR Assay”

“…Among the Lebanese population where the frequencies of the G and A alleles were reported as 77% and 23%, respectively, individuals who were found homozygous or heterozygous for − 455A had higher levels of plasma fibrinogen than those who were homozygous for − 455G ( Shammaa et al, 2008a ). Furthermore, polymorphisms in the plasminogen activator inhibitor type-1 (PAI-1) gene, including the 4G/5G polymorphism, contribute to the occurrence of thrombotic events by increasing the level of PAI-1 thus leading to excessive buildup of fibrin ( Shammaa et al, 2008b ). The data from Lebanon revealed that the frequency of the mutant 4G allele is 40.3%, with a higher rate of heterozygous individuals compared to homozygous, while the 5G allele frequency stands at 59.7% ( Shammaa et al, 2008b ).…”

“…Furthermore, polymorphisms in the plasminogen activator inhibitor type-1 (PAI-1) gene, including the 4G/5G polymorphism, contribute to the occurrence of thrombotic events by increasing the level of PAI-1 thus leading to excessive buildup of fibrin ( Shammaa et al, 2008b ). The data from Lebanon revealed that the frequency of the mutant 4G allele is 40.3%, with a higher rate of heterozygous individuals compared to homozygous, while the 5G allele frequency stands at 59.7% ( Shammaa et al, 2008b ).…”

The prevalence of PAI-1 4G/5G gene variant in Serbian population

“…PAI-1 deluje kao inhibitor endogene  brinoliti ke aktivnosti, zbog svoje sposob-nosti da inhibira aktivnost tkivnog tipa aktivatora plazminogena (t-PA), i urokinaza tipa aktivatora plazminogena (u-PA) (4)(5)(6). Gen za PAI-1 nalazi se na hromozomu 7 (7q21.3-q22.1) i sadrži 8 introna i 9 egzona (3).…”