title: Association of genetic variants of fibrinolytic system with stroke and stroke subtypes.
abstract: Genetic variants of tPA (PLAT) and PAI-1 genes have been suggested to be the risk factors for stroke. In the present case-control study we investigated the association of -7351C/T polymorphism (rs2020918) and I/D polymorphism of tPA gene and Insertion/deletion polymorphism (4G/5G) of PAI-1 gene with genetic predisposition to ischemic stroke. 516 stroke patients and 513, sex and age matched healthy controls were involved in the study. We did not find a significant association of tPA -7351C/T polymorphism and PAI-1 4G/5G polymorphism with stroke. However, in case of I/D polymorphism significant difference was observed in the genotypic distribution and allelic frequency between the stroke patients and healthy controls. DD genotype and D allele associated significantly with stroke (p=0.002 and <0.001 respectively). We also found significant association of I/D polymorphism with intracranial large artery atherosclerosis and stroke of undetermined etiology. Exploring the association between gene-gene interaction (26 combinations including the three variants) and stroke, we found that individuals with CC+4G4G+DD, CC+5G5G+ID, CT+4G5G+ID, CT+5G5G+II, CT+5G5G+ID and TT+4G5G+II had a significantly higher risk of stroke. The results of this study suggest that -7351C/T polymorphism of tPA and 4G/5G polymorphism of PAI-1 are not associated with stroke, while as DD genotype and D allele of tPA gene are important risk factors for ischemic stroke. Further we found that the subjects with different tPA and PAI genotype combinations displayed a significantly high risk for overall ischemic stroke suggesting that gene-gene interaction involving more variants may change the susceptibility of particular subjects to the disease.
authors.affiliation: Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet, Hyderabad-500016, India.
authors.forename: M Sai
authors.initials: MS
authors.lastname: Babu
authors.forename: T Surya
authors.initials: TS
authors.lastname: Prabha
authors.forename: Subhash
authors.initials: S
authors.lastname: Kaul
authors.forename: Amal
authors.initials: A
authors.lastname: Al-Hazzani
authors.forename: Gowhar
authors.initials: G
authors.lastname: Shafi
authors.forename: Sitara
authors.initials: S
authors.lastname: Roy
authors.forename: N
authors.initials: N
authors.lastname: Balakrishna
authors.forename: A
authors.initials: A
authors.lastname: Jyothy
authors.forename: Anjana
authors.initials: A
authors.lastname: Munshi
mesh_terms: D000328:Adult; D000368:Aged; D002545:Brain Ischemia / Q000235:genetics; D016022:Case-Control Studies; D004843:Epistasis, Genetic; D005260:Female; D005342:Fibrinolysis / Q000235:genetics*; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D054643:INDEL Mutation; D002537:Intracranial Arteriosclerosis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D012307:Risk Factors; D020521:Stroke / Q000235:genetics*; D010959:Tissue Plasminogen Activator / Q000235:genetics*; D055815:Young Adult
chemical_list: D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D010959:Tissue Plasminogen Activator