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Association of PAI-1 4G/5G and -844G/A gene polymorphism and changes in PAI-1/tPA levels in stroke: a case-control study.
J Stroke Cerebrovasc Dis. 2007 Jul-Aug; 16(4):153-9.JS

Abstract

Mutations in the plasminogen activator inhibitor-1 (PAI-1) gene, along with altered PAI-1 and tissue-type plasminogen activator (tPA) levels, have been implicated in stroke pathogenesis. We investigated the association of PAI-1 and tPA levels with stroke as a function of PAI-1 4G/5G and -844G/A genotypes, as well as the link between these PAI-1 gene variants and stroke risk, in a case-control study of 135 ischemic stroke patient, diagnosed according to clinical and radiologic findings and confirmed by computed tomography scan. Controls (n = 118) were age- and sex-matched and had no personal/family history of stroke. PAI-1 4G/5G and -844G/A genotyping were done by polymerase chain reaction-restriction fragment length polymorphism, and PAI-1 and tPA levels were measured by enzyme immunoassay. Significant elevation in PAI-1 and marked reduction in tPA levels were seen in stroke patients and were correlated with 4G/5G, but not with -844G/A, PAI-1 variants. Whereas the frequencies of 4G or -844A alleles were comparable between patients and controls, 4G/4G carriers had reduced risk of stroke compared with other genotypes (odds ratio [OR] = 0.54; 95% confidence interval [CI] = 0.31-0.95). The 4G/-844A haplotype also was more closely associated with reduced stroke risk (OR = 0.43; 95% CI = 0.20-0.97) than 5G/-844A or 4G/-844G haplotypes. Regression analysis demonstrated that 4G homozygosity (OR = 0.176), hypertension (OR = 6.288), and body mass index (OR = 1.325) were independent predictors of stroke. The protective effect of 4G allele against stroke suggests involvement of PAI-1 4G/5G polymorphism in stroke through a mechanism not related to fibrinolysis, possibly involving altered plaque stabilization, and/or through antagonism of tPA effects.

Authors+Show Affiliations

Research Unit of Hematological and Autoimmune Diseases, Faculty of Pharmacy, University of Monastir, Monastir, Tunisia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17689411

Citation

Saidi, Sarra, et al. "Association of PAI-1 4G/5G and -844G/A Gene Polymorphism and Changes in PAI-1/tPA Levels in Stroke: a Case-control Study." Journal of Stroke and Cerebrovascular Diseases : the Official Journal of National Stroke Association, vol. 16, no. 4, 2007, pp. 153-9.
Saidi S, Slamia LB, Mahjoub T, et al. Association of PAI-1 4G/5G and -844G/A gene polymorphism and changes in PAI-1/tPA levels in stroke: a case-control study. J Stroke Cerebrovasc Dis. 2007;16(4):153-9.
Saidi, S., Slamia, L. B., Mahjoub, T., Ammou, S. B., & Almawi, W. Y. (2007). Association of PAI-1 4G/5G and -844G/A gene polymorphism and changes in PAI-1/tPA levels in stroke: a case-control study. Journal of Stroke and Cerebrovascular Diseases : the Official Journal of National Stroke Association, 16(4), 153-9.
Saidi S, et al. Association of PAI-1 4G/5G and -844G/A Gene Polymorphism and Changes in PAI-1/tPA Levels in Stroke: a Case-control Study. J Stroke Cerebrovasc Dis. 2007 Jul-Aug;16(4):153-9. PubMed PMID: 17689411.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of PAI-1 4G/5G and -844G/A gene polymorphism and changes in PAI-1/tPA levels in stroke: a case-control study. AU - Saidi,Sarra, AU - Slamia,Lamia B, AU - Mahjoub,Touhami, AU - Ammou,Sofyan B, AU - Almawi,Wassim Y, PY - 2006/11/26/received PY - 2007/01/18/revised PY - 2007/02/14/accepted PY - 2007/8/11/pubmed PY - 2007/9/15/medline PY - 2007/8/11/entrez SP - 153 EP - 9 JF - Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association JO - J Stroke Cerebrovasc Dis VL - 16 IS - 4 N2 - Mutations in the plasminogen activator inhibitor-1 (PAI-1) gene, along with altered PAI-1 and tissue-type plasminogen activator (tPA) levels, have been implicated in stroke pathogenesis. We investigated the association of PAI-1 and tPA levels with stroke as a function of PAI-1 4G/5G and -844G/A genotypes, as well as the link between these PAI-1 gene variants and stroke risk, in a case-control study of 135 ischemic stroke patient, diagnosed according to clinical and radiologic findings and confirmed by computed tomography scan. Controls (n = 118) were age- and sex-matched and had no personal/family history of stroke. PAI-1 4G/5G and -844G/A genotyping were done by polymerase chain reaction-restriction fragment length polymorphism, and PAI-1 and tPA levels were measured by enzyme immunoassay. Significant elevation in PAI-1 and marked reduction in tPA levels were seen in stroke patients and were correlated with 4G/5G, but not with -844G/A, PAI-1 variants. Whereas the frequencies of 4G or -844A alleles were comparable between patients and controls, 4G/4G carriers had reduced risk of stroke compared with other genotypes (odds ratio [OR] = 0.54; 95% confidence interval [CI] = 0.31-0.95). The 4G/-844A haplotype also was more closely associated with reduced stroke risk (OR = 0.43; 95% CI = 0.20-0.97) than 5G/-844A or 4G/-844G haplotypes. Regression analysis demonstrated that 4G homozygosity (OR = 0.176), hypertension (OR = 6.288), and body mass index (OR = 1.325) were independent predictors of stroke. The protective effect of 4G allele against stroke suggests involvement of PAI-1 4G/5G polymorphism in stroke through a mechanism not related to fibrinolysis, possibly involving altered plaque stabilization, and/or through antagonism of tPA effects. SN - 1532-8511 UR - https://www.unboundmedicine.com/medline/citation/17689411/Association_of_PAI_1_4G/5G_and__844G/A_gene_polymorphism_and_changes_in_PAI_1/tPA_levels_in_stroke:_a_case_control_study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1052-3057(07)00036-5 DB - PRIME DP - Unbound Medicine ER -