Effect of common single nucleotide polymorphisms in COX-1 gene on related metabolic activity in diabetic patients treated with acetylsalicylic acid

INTRODUCTION: The objective of this study was to investigate the effect of common single nucleotide genomic polymorphisms in the cyclooxygenase-1 (COX-1) gene on the thromboxane A(2) (TxA(2)) metabolite concentrations in serum and urine, as well as on prostaglandin F2α (PGF2α) urinary excretion in the diabetic population on acetylsalicylic acid (ASA) therapy. MATERIAL AND METHODS: The study cohort consisted of 284 Caucasians with diabetes type 2 who had been taking ASA tablets at the dose of 75 mg/day for at least 3 months. Genotyping for the 4 selected SNPs within the COX-1 gene (two nonsynonymous-coding variants, rs3842787 [C50T, P17L] and rs5789 [C174A, L237M]; and two other synonymous SNPs, rs3842788 [G128A, Q41Q] and rs5788 [C644A]) was performed using the Sequenom iPLEX platform. RESULTS: No statistically significant results were observed for the investigated SNPs and measured metabolites in the investigated cohort of patients. Statistically significant differences in S-TxB(2) could however be observed for rs5788 in the subgroup of patients with very high S-TxB(2) concentrations. In particular, more patients who were carriers of the minor allele for this polymorphism were observed in the group with S-TxB(2) levels > 95(th) percentile, when compared with similar carriers in the group with S-TxB(2) < 95(th) percentile (20% vs. 1.1%, respectively, p < 0.001, Mann-Whitney test). CONCLUSIONS: The results of our study suggest that the four investigated common SNPs in the COX1 gene are not associated with obviously altered TxA(2) metabolism and PGF2α synthesis in the investigated diabetic cohort treated with ASA.