ABSTRACT
The majority of ischemic strokes occur because of thrombotic or thromboembolic occlusions. This forms the rationale for use of thrombolytic drugs. Out of several identified single nucleotide polymorphism [SNPs] at the Tissue-type Plasminogen Activator [tfA] locus, the-7351 CIT enhancer SNP showed closest association to tPA release rates. Functional studies have shown that this SNP affects the binding of transcription factors, and that the T allele expresses less tPA compared with the C allele as well as increased risk of myocardial infarction A recent study also reported an increased risk of ischemic stroke for the TT genotype. In the present study the possible association between ischemic stroke and the tPA-7351C>T polymorphism was investigated. Forty eight ischemic stroke patients and 48 matched control cases were recruited in a case control study.Genotyping was performed by allele discrimination analysis using the 5'nuclease assay. PCR was performed in RotorGene[TM] 6000 [Corbett Research]. Results were represented by two curves as: yellow channel represents C probe labeled by [VIC] dye; this is the wild type. Green channel represents T probe labeled by [FAM] dye; this is the mutant allele. In patients group the frequency of the low risk allele [C] of tPA gene was 57.25% and of high risk allele [T] was 42.75%. Whereas control revealed 78.13% and 21.87%, respectively. The genotype distribution was in Hardy-Weinberg equilibrium. The odds ratio for overall ischemic stroke was 2.66 [95% Cl: 1.42 to 5.01] for tPA T allele carriers. This association was independent of established risk factors. tPA-735 1 C/T enhancer polymorphism may be a risk factor for ischemic stroke. Further studies on larger populations with stratification for stroke subtypes are needed to confirm these findings. The possible association between this polymorphism and the respective plasma protein level remain to be elucidated