title: Single nucleotide polymorphism markers for low-dose aspirin-associated peptic ulcer and ulcer bleeding.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kawasaki Medical School, Matsushima Kurashiki, Okayama Prefecture, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Shiotani
authors.forename: Takahisa
authors.initials: T
authors.lastname: Murao
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Fujita
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Fujimura
authors.forename: Takashi
authors.initials: T
authors.lastname: Sakakibara
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nishio
authors.forename: Ken
authors.initials: K
authors.lastname: Haruma
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D027381:Liver-Specific Organic Anion Transporter 1; D008297:Male; D008875:Middle Aged; D027361:Organic Anion Transporters / Q000235:genetics; D010437:Peptic Ulcer / Q000139:chemically induced* / Q000235:genetics*; D010438:Peptic Ulcer Hemorrhage / Q000139:chemically induced* / Q000235:genetics*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D015238:Sulfotransferases / Q000235:genetics; D011795:Surveys and Questionnaires; D000097811:Carbohydrate Sulfotransferases
chemical_list: D001241:Aspirin; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; D010975:Platelet Aggregation Inhibitors; D015238:Sulfotransferases; D000097811:Carbohydrate Sulfotransferases; C503999:SLCO1B1 protein, human
keywords: CHST2; DMET; HMG-Co A reductase inhibitors (statins); SLCO1B; angiotensin type 1 receptor (AT1R) blockers (ARBs)