Association of genetic variants of fibrinolytic system with stroke and stroke subtypes

作者:Babu M Sai; Prabha T Surya; Kaul Subhash; Al Hazzani Amal; Shafi Gowhar; Roy Sitara; Balakrishna N; Jyothy A; Munshi Anjana*
来源:Gene, 2012, 495(1): 76-80.
DOI:10.1016/j.gene.2011.12.046

摘要

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 -7351 C/T polymorphism (rs2020918) and I/D polymorphism of tPA gene and Insertion/deletion polymorphism (4 G/5 G) 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 -7351 C/T polymorphism and PAI-1 4 G/5 G 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 %26lt;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 7351 C/T polymorphism of tPA and 4 G/5 G 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.