Bactericidal/Permeability-Increasing Fold-Containing Family B Member 4 May Be Associated with NSAID-Induced Enteropathy

Shunji Fujimori, Koya Fukunaga, Atsushi Takahashi, Taisei Mushiroda, Michiaki Kubo, Ryuzo Hanada, Mari Hayashida, Toshiyuki Sakurai, Katsuhiko Iwakiri, Choitsu Sakamoto

Research output: Contribution to journalArticle

Abstract

Background: There is considerable individual variability in nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy. Aim: To identify the SNP that is most significantly involved with NSAID-induced enteropathy. Methods: One hundred fifty human subjects who were known to have a certain degree of loxoprofen- or celecoxib-induced small-intestinal damage from a previous study were enrolled. The subjects were divided into groups based on treatments and also on the increased number of small intestinal mucosal breaks. The candidate SNP was selected by an initial analysis of GWAS among the groups in various combinations. After the initial analysis, the gene including the specified SNP was analyzed in detail using GWAS and genotype imputation. Results: After analysis, 70 subjects receiving the loxoprofen treatment and 69 subjects receiving celecoxib treatment were determined to be eligible for the analysis. The minimum p value in GWAS was detected in the analysis of 16 cases with an increase of five or more mucosal breaks and 123 controls with zero to four mucosal breaks. In the GWAS, five SNPs in the bactericidal/permeability-increasing fold-containing family B member 4 (BPIFB4) gene showed the lowest p value (p = 2.69 × 10 −7 with an odds ratio of 40.9). Of the five SNPs, four were nonsynonymous SNPs (rs2070325: V268I, rs2889732: T320N, rs11699009: F527L, rs11696307: T533I, and rs11696310: intronic). Furthermore, 23 SNPs in BPIFB4 detected by genotype imputation based on the GWAS data also showed suggestive associations (p < 1 × 10 −6 ). Conclusion: The results indicate that SNPs in BPIFB4 were associated with NSAID-induced small intestinal mucosal injury (UMIN: 000007936).

Original languageEnglish
Pages (from-to)401-408
Number of pages8
JournalDigestive Diseases and Sciences
Volume64
Issue number2
DOIs
Publication statusPublished - 15-02-2019

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Single Nucleotide Polymorphism
Permeability
Anti-Inflammatory Agents
Genome-Wide Association Study
Celecoxib
Pharmaceutical Preparations
Genotype
Genes
Odds Ratio
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Physiology
  • Gastroenterology

Cite this

Fujimori, Shunji ; Fukunaga, Koya ; Takahashi, Atsushi ; Mushiroda, Taisei ; Kubo, Michiaki ; Hanada, Ryuzo ; Hayashida, Mari ; Sakurai, Toshiyuki ; Iwakiri, Katsuhiko ; Sakamoto, Choitsu. / Bactericidal/Permeability-Increasing Fold-Containing Family B Member 4 May Be Associated with NSAID-Induced Enteropathy. In: Digestive Diseases and Sciences. 2019 ; Vol. 64, No. 2. pp. 401-408.
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title = "Bactericidal/Permeability-Increasing Fold-Containing Family B Member 4 May Be Associated with NSAID-Induced Enteropathy",
abstract = "Background: There is considerable individual variability in nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy. Aim: To identify the SNP that is most significantly involved with NSAID-induced enteropathy. Methods: One hundred fifty human subjects who were known to have a certain degree of loxoprofen- or celecoxib-induced small-intestinal damage from a previous study were enrolled. The subjects were divided into groups based on treatments and also on the increased number of small intestinal mucosal breaks. The candidate SNP was selected by an initial analysis of GWAS among the groups in various combinations. After the initial analysis, the gene including the specified SNP was analyzed in detail using GWAS and genotype imputation. Results: After analysis, 70 subjects receiving the loxoprofen treatment and 69 subjects receiving celecoxib treatment were determined to be eligible for the analysis. The minimum p value in GWAS was detected in the analysis of 16 cases with an increase of five or more mucosal breaks and 123 controls with zero to four mucosal breaks. In the GWAS, five SNPs in the bactericidal/permeability-increasing fold-containing family B member 4 (BPIFB4) gene showed the lowest p value (p = 2.69 × 10 −7 with an odds ratio of 40.9). Of the five SNPs, four were nonsynonymous SNPs (rs2070325: V268I, rs2889732: T320N, rs11699009: F527L, rs11696307: T533I, and rs11696310: intronic). Furthermore, 23 SNPs in BPIFB4 detected by genotype imputation based on the GWAS data also showed suggestive associations (p < 1 × 10 −6 ). Conclusion: The results indicate that SNPs in BPIFB4 were associated with NSAID-induced small intestinal mucosal injury (UMIN: 000007936).",
author = "Shunji Fujimori and Koya Fukunaga and Atsushi Takahashi and Taisei Mushiroda and Michiaki Kubo and Ryuzo Hanada and Mari Hayashida and Toshiyuki Sakurai and Katsuhiko Iwakiri and Choitsu Sakamoto",
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Fujimori, S, Fukunaga, K, Takahashi, A, Mushiroda, T, Kubo, M, Hanada, R, Hayashida, M, Sakurai, T, Iwakiri, K & Sakamoto, C 2019, 'Bactericidal/Permeability-Increasing Fold-Containing Family B Member 4 May Be Associated with NSAID-Induced Enteropathy' Digestive Diseases and Sciences, vol. 64, no. 2, pp. 401-408. https://doi.org/10.1007/s10620-018-5349-0

Bactericidal/Permeability-Increasing Fold-Containing Family B Member 4 May Be Associated with NSAID-Induced Enteropathy. / Fujimori, Shunji; Fukunaga, Koya; Takahashi, Atsushi; Mushiroda, Taisei; Kubo, Michiaki; Hanada, Ryuzo; Hayashida, Mari; Sakurai, Toshiyuki; Iwakiri, Katsuhiko; Sakamoto, Choitsu.

In: Digestive Diseases and Sciences, Vol. 64, No. 2, 15.02.2019, p. 401-408.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Bactericidal/Permeability-Increasing Fold-Containing Family B Member 4 May Be Associated with NSAID-Induced Enteropathy

AU - Fujimori, Shunji

AU - Fukunaga, Koya

AU - Takahashi, Atsushi

AU - Mushiroda, Taisei

AU - Kubo, Michiaki

AU - Hanada, Ryuzo

AU - Hayashida, Mari

AU - Sakurai, Toshiyuki

AU - Iwakiri, Katsuhiko

AU - Sakamoto, Choitsu

PY - 2019/2/15

Y1 - 2019/2/15

N2 - Background: There is considerable individual variability in nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy. Aim: To identify the SNP that is most significantly involved with NSAID-induced enteropathy. Methods: One hundred fifty human subjects who were known to have a certain degree of loxoprofen- or celecoxib-induced small-intestinal damage from a previous study were enrolled. The subjects were divided into groups based on treatments and also on the increased number of small intestinal mucosal breaks. The candidate SNP was selected by an initial analysis of GWAS among the groups in various combinations. After the initial analysis, the gene including the specified SNP was analyzed in detail using GWAS and genotype imputation. Results: After analysis, 70 subjects receiving the loxoprofen treatment and 69 subjects receiving celecoxib treatment were determined to be eligible for the analysis. The minimum p value in GWAS was detected in the analysis of 16 cases with an increase of five or more mucosal breaks and 123 controls with zero to four mucosal breaks. In the GWAS, five SNPs in the bactericidal/permeability-increasing fold-containing family B member 4 (BPIFB4) gene showed the lowest p value (p = 2.69 × 10 −7 with an odds ratio of 40.9). Of the five SNPs, four were nonsynonymous SNPs (rs2070325: V268I, rs2889732: T320N, rs11699009: F527L, rs11696307: T533I, and rs11696310: intronic). Furthermore, 23 SNPs in BPIFB4 detected by genotype imputation based on the GWAS data also showed suggestive associations (p < 1 × 10 −6 ). Conclusion: The results indicate that SNPs in BPIFB4 were associated with NSAID-induced small intestinal mucosal injury (UMIN: 000007936).

AB - Background: There is considerable individual variability in nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy. Aim: To identify the SNP that is most significantly involved with NSAID-induced enteropathy. Methods: One hundred fifty human subjects who were known to have a certain degree of loxoprofen- or celecoxib-induced small-intestinal damage from a previous study were enrolled. The subjects were divided into groups based on treatments and also on the increased number of small intestinal mucosal breaks. The candidate SNP was selected by an initial analysis of GWAS among the groups in various combinations. After the initial analysis, the gene including the specified SNP was analyzed in detail using GWAS and genotype imputation. Results: After analysis, 70 subjects receiving the loxoprofen treatment and 69 subjects receiving celecoxib treatment were determined to be eligible for the analysis. The minimum p value in GWAS was detected in the analysis of 16 cases with an increase of five or more mucosal breaks and 123 controls with zero to four mucosal breaks. In the GWAS, five SNPs in the bactericidal/permeability-increasing fold-containing family B member 4 (BPIFB4) gene showed the lowest p value (p = 2.69 × 10 −7 with an odds ratio of 40.9). Of the five SNPs, four were nonsynonymous SNPs (rs2070325: V268I, rs2889732: T320N, rs11699009: F527L, rs11696307: T533I, and rs11696310: intronic). Furthermore, 23 SNPs in BPIFB4 detected by genotype imputation based on the GWAS data also showed suggestive associations (p < 1 × 10 −6 ). Conclusion: The results indicate that SNPs in BPIFB4 were associated with NSAID-induced small intestinal mucosal injury (UMIN: 000007936).

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