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

Abstract

IntroductionThe 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 methodsThe 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.ResultsNo 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 > 95th percentile, when compared with similar carriers in the group with S-TxB2 < 95th percentile (20% vs. 1.1%, respectively, p < 0.001, Mann-Whitney test).ConclusionsThe 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.

The pharmacogenetic control of antiplatelet response: candidate genes andCYP2C19

“…Although it was initially reported that healthy individuals with the minor haplotype (c.[-842G;50T]) had better on-treatment inhibition of prostaglandin H 2 and AA-induced platelet aggregation compared to those with the common haplotype (c.[-842A;50C]) [19], subsequent studies on stable CAD patients identified the c.-842G allele to actually be associated with aspirin resistance and non-responsiveness based on AA-induced platelet aggregation and serum TXB 2 levels [20]. More recent studies on the COX1 c.-842A>G and c.50C>T variants using several different aspirin response phenotypes and platelet function tests observed no significant association between these variants and TBX 2 levels, platelet aggregation, or cardiovascular outcomes [21–28], including a recent systematic review [29]. Consequently, the available evidence does not support a clinically relevant role for COX1 variants in aspirin response.…”