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Single nucleotide polymorphism markers for low‐dose aspirin‐associated peptic ulcer and ulcer bleeding
Author(s) -
Shiotani Akiko,
Murao Takahisa,
Fujita Yoshihiko,
Fujimura Yoshinori,
Sakakibara Takashi,
Nishio Kazuto,
Haruma Ken
Publication year - 2014
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.12770
Subject(s) - medicine , gastroenterology , aspirin , single nucleotide polymorphism , haplotype , genotype , allele , gene , genetics , biology
Background and Aim In our previous study, the SLCO 1 B 1 521 TT genotype and the SLCO 1 B 1 *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 A ffymetrix DME P lus P remier P ack. S LCO 1 B 1 *1b haplotype and candidate genotypes of genes associated with ulcer bleeding or small bowel bleeding identified by genome‐wide analysis were determined using T aq M an SNP G enotyping A ssay 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 SLCO 1 B 1 *1b haplotype and CHST 2 2082 T allele were significantly greater in patients with peptic ulcer and ulcer bleeding compared to the controls. After adjustment for significant factors, the SLCO 1 B 1 *1b haplotype was associated with peptic ulcer ( OR 2.20, 95% CI 1.24–3.89) and CHST 2 2082 T allele with ulcer bleeding (2.57, 1.07–6.17). Conclusion The CHST 2 2082 T allele as well as SLCO 1 B 1*1b haplotype may identify patients at increased risk for aspirin‐induced peptic ulcer or ulcer bleeding.