A novel gene associated with small bowel bleeding in patients taking low-dose aspirin

• Published in: Digestive and liver disease Vol. 53; no. 7; pp. 841 - 845
• Main Authors: Handa, Yukiko, Fukushima, Shinya, Yo, Shogen, Osawa, Motoyasu, Murao, Takahisa, Handa, Osamu, Matsumoto, Hiroshi, Umegaki, Eiji, Sakakibara, Takashi, Shiotani, Akiko
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.07.2021
• Subjects: Aged; Aspirin - administration & dosage; Aspirin - adverse effects; Capsule Endoscopy; CYP4F11; Cytochrome P450 Family 4 - genetics; Female; Gastrointestinal Hemorrhage - chemically induced; Gastrointestinal Hemorrhage - genetics; Genome-Wide Association Study; Glutathione S-Transferase pi - genetics; GSTP-1; Humans; Intestinal Diseases - chemically induced; Intestinal Diseases - genetics; Intestine, Small - pathology; Male; Pharmacogenomic Variants - genetics; Polymorphism, Single Nucleotide - genetics; Propensity Score; Risk Factors; Single nucleotide polymorphism; Small bowel bleeding; Single nucleotide polymorphism; CYP4F11; GSTP-1; Small bowel bleeding
• ISSN: 1590-8658; 1878-3562; 1878-3562
• DOI: 10.1016/j.dld.2021.04.038

We have previously revealed the clinical factors and genetic polymorphisms associated with gastrointestinal mucosal injury and bleeding, induced by low-dose aspirin (LDA). After performing genome-wide analysis of single nucleotide polymorphisms (SNPs) using the Drug Metabolizing Enzymes and Transporters (DMET) system among drug metabolism and transporter genes, certain SNPs were found to increase the risk for LDA-induced small bowel bleeding. The aim of this study was to identify the SNPs involved in LDA-induced small bowel bleeding. Subjects were patients taking LDA, with small bowel bleeding diagnosed using capsule endoscopy. We investigated the clinical characteristics and the previously identified SNPs, that were examined by the DNA direct sequence method. 56 patients with bleeding and 410 controls taking LDA were enrolled. The risk factors associated with small bowel bleeding included smoking, cerebrovascular diseases, chronic renal failure, non-steroidal anti-inflammatory drug (NSAID) or anticoagulants combination, and two SNPs (CYP4F11 20043G>A (D446N) rs1060463, GSTP1 313A>G rs1695). After propensity score matching, GSTP1 rs1695 was significantly associated with small bowel bleeding. The GSTP1 SNP may be a predictive marker for small bowel bleeding among patients taking LDA.