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

Autor: Ryuzo Hanada, Katsuhiko Iwakiri, Choitsu Sakamoto, Atsushi Takahashi, Toshiyuki Sakurai, Mari Hayashida, Koya Fukunaga, Shunji Fujimori, Michiaki Kubo, Taisei Mushiroda
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Male
Physiology
Gastroenterology
Capsule Endoscopy
law.invention
chemistry.chemical_compound
0302 clinical medicine
Transplant surgery
law
Intestine
Small
GWAS
Enteropathy
Intestinal Mucosa
skin and connective tissue diseases
media_common
Phenylpropionates
Anti-Inflammatory Agents
Non-Steroidal
Middle Aged
NSAID
030220 oncology & carcinogenesis
BPI
Intercellular Signaling Peptides and Proteins
030211 gastroenterology & hepatology
Original Article
Female
musculoskeletal diseases
Drug
Adult
medicine.medical_specialty
media_common.quotation_subject
digestive system
Polymorphism
Single Nucleotide
03 medical and health sciences
Capsule endoscopy
Internal medicine
medicine
Humans
Nonsteroidal
business.industry
Hepatology
medicine.disease
Phosphoproteins
digestive system diseases
Small intestinal injury
Intestinal Diseases
chemistry
Permeability (electromagnetism)
Celecoxib
business
Genome-Wide Association Study
Zdroj: Digestive Diseases and Sciences
ISSN: 1573-2568
0163-2116
Popis: 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
Databáze: OpenAIRE
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