Key result
SLCO1B1*1b haplotype linked to ~120% greater peptic ulcer risk and CHST2 allele to ulcer bleeding.
Why the study?
Pharmacogenomic profiles associated with low-dose aspirin-induced peptic ulcer and ulcer bleeding were not fully characterized.
Do the SLCO1B1*1b haplotype and CHST2 2082 T allele increase the risk of peptic ulcer and ulcer bleeding in patients taking low-dose aspirin for cardiovascular diseases?
Case-Control (n=593)
Do the SLCO1B1*1b haplotype and CHST2 2082 T allele increase the risk of peptic ulcer and ulcer bleeding in patients taking low-dose aspirin for cardiovascular diseases?
Odds Ratio: 2.2 (95% CI 1.24–3.89)
The SLCO1B1*1b haplotype and CHST2 2082 T allele may identify patients at increased risk for peptic ulcer or ulcer bleeding when taking low-dose aspirin for cardiovascular disease.
May flag higher GI risk in aspirin users for CV disease; hypothesis-generating and should not yet change practice.
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. SLCO1B1*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.
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Shiotani et al. (2014) conducted a case-control in Low-dose aspirin-associated peptic ulcer and ulcer bleeding (n=593). SLCO1B1*1b haplotype and CHST2 2082 T allele vs. Controls without the genetic markers was evaluated on Peptic ulcer (OR 2.20, 95% CI 1.24-3.89). The SLCO1B1*1b haplotype was significantly associated with peptic ulcer (OR 2.20; 95% CI 1.24-3.89), and the CHST2 2082 T allele was associated with ulcer bleeding (OR 2.57; 95% CI 1.07-6.17).
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