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30 December 2008

The effect of an exon 12 polymorphism of the human thromboxane synthase (CYP5A1) gene in stroke patients

Maria KimouliBEF, Viktoras GourvasB, Xanthippi KonstantoudakiBCD, Maria BastaB, Spiros MiyakisABCDE, Demetrios A. SpandidosADEG

Med Sci Monit 2009; 15(1): BR30-35 :: ID: 869530

Abstract

Background
To examine the prevalence of an exon 12 polymorphism on the human Thromboxane synthase (CYP5A1) gene.
Material and Method
Using sequence-specific PCR, we examined the allelic prevalence in 237 Greek patients with ischemic strokes and in 171 controls. In addition, we compared the CYP5A1 allelic prevalence in 71 patients with stroke recurrence despite Aspirin use, in comparison with patients who have not experienced recurrent stroke while taking Aspirin.
Results
The frequencies of the CYP5A1*9 mutant (substitution of guanine by adenine near the heme-binding catalytic domain) and of the wild-type allele were 0.197 and 0.803, respectively; they did not differ significantly between stroke patients and controls. The wild-type allele was more frequent in the Cretan population compared to continental Greece (OR 1.80, 95% CI 1.19-2.74). The wild-type allele was more frequent among hypertensive and less frequent among diabetic stroke sufferers, respectively. The CYP5A1*9 mutant was significantly more prevalent among stroke patients with history of previous cerebrovascular attacks (p<0.01); and among those who failed secondary Aspirin prophylaxis even after adjusting for the common risk factors for cardiovascular disease (OR 1.49, 95% CI 1.06-2.11).
Conclusions
Allelic prevalence of the CYP5A1 exon 12 might differ between geographic areas within the same ethnic group, and is associated with particular characteristics of stroke patients. Allele mutations can abolish the enzymatic activity of thromboxane synthase, via impaired heme binding, associated with defective response to Aspirin used as secondary prevention, an effect independent from the conventional risk factors for cerebrovascular disease.

Keywords: Stroke - enzymology, Spectrophotometry, Ultraviolet, Thromboxane-A Synthase - metabolism, Polymorphism, Single Nucleotide, Mutation, Missense - genetics, Heme - metabolism, Greece, Genotype, Gene Frequency, Exons - genetics, DNA Primers - genetics

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750