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


Journal

Digestive diseases and sciences
ISSN: 1573-2568
Titre abrégé: Dig Dis Sci
Pays: United States
ID NLM: 7902782

Informations de publication

Date de publication:
02 2019
Historique:
received: 05 07 2018
accepted: 19 10 2018
pubmed: 1 11 2018
medline: 26 3 2019
entrez: 1 11 2018
Statut: ppublish

Résumé

There is considerable individual variability in nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy. To identify the SNP that is most significantly involved with NSAID-induced enteropathy. 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. 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 The results indicate that SNPs in BPIFB4 were associated with NSAID-induced small intestinal mucosal injury (UMIN: 000007936).

Sections du résumé

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
CONCLUSION
The results indicate that SNPs in BPIFB4 were associated with NSAID-induced small intestinal mucosal injury (UMIN: 000007936).

Identifiants

pubmed: 30377885
doi: 10.1007/s10620-018-5349-0
pii: 10.1007/s10620-018-5349-0
pmc: PMC6514250
doi:

Substances chimiques

Anti-Inflammatory Agents, Non-Steroidal 0
BPIFB4 protein, human 0
Intercellular Signaling Peptides and Proteins 0
Phenylpropionates 0
Phosphoproteins 0
loxoprofen 3583H0GZAP
Celecoxib JCX84Q7J1L

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

401-408

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Auteurs

Shunji Fujimori (S)

Department of Gastroenterology, Graduate School of Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan. s-fujimori@nms.ac.jp.

Koya Fukunaga (K)

RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.

Atsushi Takahashi (A)

RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Department of Genomic Medicine, Research Institute, National Cerebral and Cardiovascular Center, Osaka, Japan.

Taisei Mushiroda (T)

RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.

Michiaki Kubo (M)

RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.

Ryuzo Hanada (R)

Sumida Hospital, SOUSEIKAI, Tokyo, Japan.

Mari Hayashida (M)

The Third Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan.

Toshiyuki Sakurai (T)

Department of Gastroenterology and Hepatology, National Center for Global Health and Medicine, Tokyo, Japan.

Katsuhiko Iwakiri (K)

Department of Gastroenterology, Graduate School of Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.

Choitsu Sakamoto (C)

Department of Gastroenterology, Graduate School of Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.

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Classifications MeSH