Efffect of common single nucleotide polymorphisms in COX-1 gene on rellated metabolliic actiiviity iin diiabetiic 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 A₂ (TxA₂) 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-TxB₂ could however be observed for rs5788 in the subgroup of patients with very high S-TxB₂ concentrations. In particular, more patients who were carriers of the minor allele for this polymorphism were observed in the group with S-TxB₂ levels > 95^th percentile, when compared with similar carriers in the group with S-TxB₂ < 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 TxA₂ metabolism and PGF2α synthesis in the investigated diabetic cohort treated with ASA.