RESUMO
BACKGROUND: Cyclooxygenase 1 (COX-1), COX-2, and HO-1 are involved in the process of aspirin's effect. The genetic susceptibility of these enzymes to aspirin resistance (AR) is unclear. METHODS: A total of 431 patients took aspirin. Using arachidonic acid-induced light transmittance aggregation combined with adenosine diphosphate-induced light transmittance aggregation, 36 participants served for AR, 164 participants for semi-AR, and 231 participants for aspirin sensitivity (AS). The AR with 9 single-nucleotide polymorphism in COX-1, COX-2, and HO-1 genes was investigated. RESULTS: COX-1 rs1330344 (-1676A>G) is associated with AR. G-Allele carriers significantly increased the risk of AR. For patients with AS as control, P is .02 (odds ratio [OR] = 1.77, confidence interval [CI]: 1.07-2.92). For patients with semi-AR as control, P is .05. HO-1 rs2071746 (-413A>T) is associated with AR. T-Allele carriers significantly increased the risk of AR. For patients with AS as control, P is .04 (OR = 1.70, CI: 1.02-2.79). For patients with semi-AR as control, P is .05 (OR = 1.68, CI: 1.00-2.80). CONCLUSION: rs2071746 in HO-1 gene, rs1330344 in COX-1 gene contribute to AR.
Assuntos
Aspirina/farmacologia , Ciclo-Oxigenase 1/genética , Heme Oxigenase-1/genética , Idoso , Povo Asiático , Plaquetas/química , Plaquetas/citologia , Plaquetas/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase/farmacologia , Resistência a Medicamentos , Feminino , Humanos , Masculino , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia , Polimorfismo de Nucleotídeo Único , Espalhamento de RadiaçãoRESUMO
OBJECTIVE: To investigate whether cyclooxygenase-1 (COX-1) haplotype is associated, with aspirin resistance. METHODS: The participants were 431 old Chinese Han patients with cardiovascular and cerebrovascular diseases who took aspirin. The 59 patients with aspirin resistance (AR) by light transmittance aggregation acted as the cases; the 372 aspirin-sensitive patients were the controls. The relationships between AR and 6 single nucleotide polymorphisms (SNPs) in COX-1 gene. rs1888943 (8759C/T), rs1330344 (1676A/G), rs3842787 (exon2, 50C/T, p.Pro17Leu), rs5787 (exon 4, 323G/A, p. ARg108Gln), rs5789 (exon7, 709C/A, p. Leu237Met) and rs5794 (exonl0, 1330G/A, p.Va1481Ile) were investigated by the USA Sequenom high-throughput single nucleotide polymorphisms (SNP) genotyping systems. RESULTS: In this case-control trial, the frequency of mutant CGCGCC-haplotype in case was 0.48 (57/118) and in control was 0.39 (286/742), which was significantly higher than that of the control group (P < or = 0.05). CONCLUSION: COX-1 haplotype is associated with aspirin resistance in old Chinese Han patients with cardio-cerebrovascular diseases, mutant CGCGCC-haplotype carriers of COX-1 has a significant significantly increased risk of AR.