The Role of PAI-1 4G/5G Promoter Polymorphism and Its Levels in the Development of Ischemic Stroke in Young Indian Population

Abstract

The plasminogen activator inhibitor-1 (PAI-1) gene has been found to be associated with the pathogenesis and progression of vascular diseases including stroke. A 4G/5G, PAI-1 gene polymorphism has been found to be associated with the plasma PAI-1 levels in different ethnic populations but results are still controversial. The aim of this study was to determine the potential association of 4G/5G polymorphism and plasma PAI-1 levels in the development of ischemic stroke (IS) in young Asian Indians. One hundred patients with IS and an equal number of age-and sex-matched controls were studied. The 4G/5G polymorphism was genotyped in the study population through allele-specific polymerase chain reaction. Plasma PAI-1 levels were evaluated using a commercial kit. The PAI-1 levels were significantly higher in patients when compared to the controls (P ¼ .03). The variant 4G allele for the PAI-I 4G/5G polymorphism showed both genotypic (P ¼ .0013, w 2 ¼ 10.303; odds ratio [OR] ¼ 3.75) as well as allelic association (P ¼ .0004, w 2 ¼ 12.273; OR ¼ 1.99) with IS. The homozygous variant 4G/4G also was found to be associated with the higher PAI-1 levels (0.005). The variant allele 4G of PAI-1 4G/5G polymorphism and higher plasma PAI-1 levels were found to be significantly associated with IS in young Asian Indians.

Correlation Between PAI-1 Gene 4G/5G Polymorphism and the Risk of Thrombosis in Ph Chromosome-Negative Myeloproliferative Neoplasms

“… 34 – 36 Tofler et al 37 prospectively investigated 3203 patients without cardiovascular diseases, and found out that the incidence of cardiovascular events was higher in patients with high PAI-1 levels. Akhter et al 38 reported that the increase in PAI-1 activity and genotype 4G4G were related to the occurrence of ischemic stroke in Indian population. Prabhudesai A et al 39 studies also showed that 4G4G genotype was an independent risk factor for DVT.…”

Lack of Associations BetweenPAI-1andFXIIIPolymorphisms and Arterial Ischemic Stroke in Children: A Systematic Review and Meta-Analysis

“…10 However, some discrepancies concerning this polymorphism can be found in the literature. Some of the authors found relations between 4G/ 4G genotype and PAI-1 level 4,5 while others did not. 11 Hindorff et al 12 and Sarecka et al 8 found that the 5G allele of PAI-1 gene but not the 4G allele to be a risk factor for CAD, especially in women.…”

“…The study based on young Indian adults (aged up to 45 years) showed that both 4G allele and 4G/4G genotype of PAI-1 gene were associated with increased risk of ischemic stroke. 16 On the other hand, Ranellou et al 17 demonstrated higher frequency of the 4G/5G genotype of the PAI polymorphism in young adults with stroke than in healthy controls. The authors suggested also protective role of 5G/5G genotype.…”

“…Numerous polymorphic variants of genes encoding proteins involved in the coagulation cascade, lipidrelated traits, or homocysteine metabolism are suggested to be related to AIS, both in adults and children. [2][3][4][5][6][7] Polymorphisms within genes of plasminogen activator inhibitor (PAI-1) or coagulation factors FII, FV, FVII, and FXIII are at increasing interests. [2][3][4][5] The insertion/deletion (-675_-674insG) polymorphism is located in the promoter region of PAI-1 gene and was found to increase the risk of myocardial infarction and coronary artery disease (CAD).…”

“…[2][3][4][5][6][7] Polymorphisms within genes of plasminogen activator inhibitor (PAI-1) or coagulation factors FII, FV, FVII, and FXIII are at increasing interests. [2][3][4][5] The insertion/deletion (-675_-674insG) polymorphism is located in the promoter region of PAI-1 gene and was found to increase the risk of myocardial infarction and coronary artery disease (CAD). 8,9 The 4G/4G genotype was shown to increase PAI-1 activity in plasma since 4G allele binds only activator of PAI-1 transcription.…”