Single nucleotide polymorphism markers for low‐dose aspirin‐associated peptic ulcer and ulcer bleeding. (December 2014) - Shiotani, Akiko
Abstract: Background and Aim: In our previous study, the SLCO1B1 521TT genotype and the SLCO1B1 *1b haplotype were significantly associated with the risk of peptic ulcer in patients taking low‐dose aspirin (LDA). The aim of the present study was to investigate pharmacogenomic profile of LDA‐induced peptic ulcer and ulcer bleeding. Methods: Patients taking 100 mg of enteric‐coated aspirin for cardiovascular diseases and with a peptic ulcer or ulcer bleeding and patients who also participated in endoscopic surveillance were studied. Genome‐wide analysis of single nucleotide polymorphisms (SNPs) was performed using the Affymetrix DME Plus Premier Pack. S LCO 1B1 *1b haplotype and candidate genotypes of genes associated with ulcer bleeding or small bowel bleeding identified by genome‐wide analysis were determined using TaqMan SNP Genotyping Assay kits, polymerase chain reaction‐restriction fragment length polymorphism, and direct sequencing. Results: Of 593 patients enrolled, 111 patients had a peptic ulcer and 45 had ulcer bleeding. The frequencies of the SLCO1B1 *1b haplotype and CHST2 2082 T allele were significantly greater in patients with peptic ulcer and ulcer bleeding compared to the controls. After adjustment for significant factors, the SLCO1B1 *1b haplotype was associated with peptic ulcer (OR 2.20, 95% CI 1.24–3.89) and CHST2 2082 T allele with ulcer bleeding (2.57, 1.07–6.17). Conclusion: The CHST2 2082 T allele as well as SLCO1B1*1b haplotype may identify patients at increased risk for aspirin‐induced peptic ulcer or ulcer bleeding.