title: Novel single nucleotide polymorphism markers for low dose aspirin-associated small bowel bleeding.
abstract: BACKGROUND
  Aspirin-induced enteropathy is now increasingly being recognized although the pathogenesis of small intestinal damage induced by aspirin is not well understood and related risk factors have not been established.
  
  
  OBJECTIVE
  To investigate pharmacogenomic profile of low dose aspirin (LDA)-induced small bowel bleeding.
  
  
  METHODS
  Genome-wide analysis of single nucleotide polymorphisms (SNPs) was performed using the Affymetrix DMET™ Plus Premier Pack. Genotypes of candidate genes associated with small bowel bleeding were determined using TaqMan SNP Genotyping Assay kits and direct sequencing.
  
  
  RESULTS
  In the validation study in overall 37 patients with small bowel bleeding and 400 controls, 4 of 27 identified SNPs: CYP4F11 (rs1060463) GG (p=0.003), CYP2D6 (rs28360521) GG (p=0.02), CYP24A1 (rs4809957) T allele (p=0.04), and GSTP1 (rs1695) G allele (p=0.04) were significantly more frequent in the small bowel bleeding group compared to the controls. After adjustment for significant factors, CYP2D6 (rs28360521) GG (OR 4.11, 95% CI. 1.62 -10.4) was associated with small bowel bleeding.
  
  
  CONCLUSIONS
  CYP4F11 and CYP2D6 SNPs may identify patients at increased risk for aspirin-induced small bowel bleeding.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kawasaki Medical School, Kurashiki City, Okayama, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Shiotani
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kawasaki Medical School, Kurashiki City, Okayama, Japan.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Murao
authors.affiliation: Department of Genome Biology, Kinki University Faculty of Medicine, Sayama City, Osaka, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Fujita
authors.affiliation: Department of Gastroenterology, Sakakibara Heart Institute of Okayama, Okayama City, Okayama, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Fujimura
authors.affiliation: Department of Gastroenterology, Sakakibara Heart Institute of Okayama, Okayama City, Okayama, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sakakibara
authors.affiliation: Department of Genome Biology, Kinki University Faculty of Medicine, Sayama City, Osaka, Japan.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nishio
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kawasaki Medical School, Kurashiki City, Okayama, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Haruma
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced* / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics*; D023281:Genomics; D006801:Humans; D007421:Intestine, Small / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide
chemical_list: D005819:Genetic Markers; D001241:Aspirin