Novel Single Nucleotide Polymorphism Markers for Low Dose Aspirin-Associated Small Bowel Bleeding

Akiko Shiotani,Kazuto Nishio,Yoshinori Fujimura,Takahisa Murao,Ken Haruma,Takashi Sakakibara,Yoshihiko Fujita,Vince Grolmusz

doi:10.1371/journal.pone.0084244

Akiko Shiotani, Kazuto Nishio + Show 6 more

Open Access

https://doi.org/10.1371/journal.pone.0084244

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Journal: PloS one	Publication Date: Dec 18, 2013
Citations: 47	License type: CC BY 4.0

Affiliation: Kawasaki Medical School, Kindai University

Abstract

BackgroundAspirin-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. AimTo investigate pharmacogenomic profile of low dose aspirin (LDA)-induced small bowel bleeding. MethodsGenome-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. ResultsIn 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. ConclusionsCYP4F11 and CYP2D6 SNPs may identify patients at increased risk for aspirin-induced small bowel bleeding.

Highlights

Aspirin had long been regarded as safe beyond the duodenum because of its rapid absorption and lack of an enterohepatic recirculation [1]
Our study attempted to identify genetic risk factors associated with small bowel bleeding
27 candidate single nucleotide polymorphisms (SNPs) of 23 genes were identified by DMETTM Plus GeneChip array, in our validation study, low dose aspirin (LDA) associated small bowel bleeding occurred more often in the patients carrying the GG homo-genotypes of CYP4F11 or CYP2D6, the patients carrying T allele of CYP24A1(rs4809957), or G allele of GSTP1

Summary

Introduction

Aspirin had long been regarded as safe beyond the duodenum because of its rapid absorption and lack of an enterohepatic recirculation [1]. In recent studies, small bowel injury and enteropathy associated with low dose aspirin (LDA) are increasingly being recognized [2,3,4,5]. In a recent Japanese retrospective cohort study of patients taking LDA, the incidence of overt GI bleeding and suspected of small bowel blood loss was 3.9% (upper GI 3.1%, colon 0.7%, and small bowel 0%) and 1.4%, respectively [6]. The pathogenesis and risk factors for small bowel damage induced by aspirin are not well understood making prevention difficult. Conclusions: CYP4F11 and CYP2D6 SNPs may identify patients at increased risk for aspirin-induced small bowel bleeding

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