Novel single nucleotide polymorphism markers for low dose aspirin-associated small bowel bleeding

Akiko Shiotani; Takahisa Murao; Yoshihiko Fujita; Yoshinori Fujimura; Takashi Sakakibara; Kazuto Nishio; Ken Haruma

doi:10.1371/journal.pone.0084244

Novel single nucleotide polymorphism markers for low dose aspirin-associated small bowel bleeding

PLoS One. 2013 Dec 18;8(12):e84244. doi: 10.1371/journal.pone.0084244. eCollection 2013.

Authors

Akiko Shiotani¹, Takahisa Murao¹, Yoshihiko Fujita², Yoshinori Fujimura³, Takashi Sakakibara³, Kazuto Nishio², Ken Haruma¹

Affiliations

¹ Division of Gastroenterology, Department of Internal Medicine, Kawasaki Medical School, Kurashiki City, Okayama, Japan.
² Department of Genome Biology, Kinki University Faculty of Medicine, Sayama City, Osaka, Japan.
³ Department of Gastroenterology, Sakakibara Heart Institute of Okayama, Okayama City, Okayama, Japan.

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.

Aim: 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Aspirin / adverse effects*
Dose-Response Relationship, Drug
Female
Gastrointestinal Hemorrhage / chemically induced*
Gastrointestinal Hemorrhage / genetics*
Genetic Markers / genetics*
Genomics
Humans
Intestine, Small / drug effects*
Male
Middle Aged
Pharmacogenetics
Polymorphism, Single Nucleotide*

Substances

Genetic Markers
Aspirin

Grants and funding

This study was supported by Grant-in-Aid for Scientific Research (C) 23590930 and Research Project Grant (23B-11, 24B-80, and 25B-36) from Kawasaki Medical School. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.