Thromboxane synthase (CYP5A1) catalyzes the conversion of prostaglandin H2 to thromboxane A2, a potent mediator of platelet aggregation, vasoconstriction and bronchoconstriction. It has been implicated in the patho-physiological process of a variety of diseases, such as atherosclerosis, myocardial infarction, stroke and asthma. Variations of the CYP5A1 gene may play an important role in human diseases, therefore, we performed screening for the prevalence of exon12 polymorphism of the human CYP5A1 gene among Egyptian normal and stroke patients. Using sequence-specific PCR, we examined the allelic prevalence in 70 Egyptian patients with ischemic strokes and in 70 controls. In addition, we compared the CYP5A1 allelic prevalence in 30 patients with stroke recurrence despite Aspirin use, in comparison with patients who have not experienced recurrent stroke while taking Aspirin. The frequencies of the CYP5A1*9 mutant (substitution of guanine by adenine near the hemebinding catalytic domain) and of the wild-type allele were 0.197(19.7%) and 0.803 (80.3%) respectively; they did not differ significantly between stroke patients and controls. The CYP5A119 mutant was significantly more prevalent among stroke patients with history of previous cerebrovascular attacks; even after adjusting for the common risk factors for cardiovascular disease [odds ratio (OR) 1.73, 95%, confidence interval (CI) 1.10?2.73; p=0.017]. Among stroke patients, the presence of the CYP5A1 wild type allele was more frequent among the hypertensives (OR 1.68, 95% CI, 1.01?2.79; p=0.045), and less frequent among the diabetics (OR 0.55, 95%, CI 0.36?0.84; p=0.006). Also, the CYP5A1*9 mutant was significantly more prevalent among those, who failed secondary Aspirin prophylaxis compared to those with successful secondary Aspirin prophylaxis (OR 1.49, 95%, CI 1.06?2.11). This study provides evidence for high prevalence of the CYP5A1*9 mutant among the Egyptian population. The presence of a mutant, affecting the heme-binding site of the enzyme, is possibly associated with recurrent cerebrovascular attacks in patients who fail secondary prophylaxis with Aspirin, an effect independent of the conventional risk factors for cerebrovascular disease.

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