Dataset Information

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?

SUBMITTER: Fujimori S

PROVIDER: S-EPMC6514250 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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

Fujimori Shunji S Fukunaga Koya K Takahashi Atsushi A Mushiroda Taisei T Kubo Michiaki M Hanada Ryuzo R Hayashida Mari M Sakurai Toshiyuki T Iwakiri Katsuhiko K Sakamoto Choitsu C

Digestive diseases and sciences 20181030 2

<h4>Background</h4>There is considerable individual variability in nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy.<h4>Aim</h4>To identify the SNP that is most significantly involved with NSAID-induced enteropathy.<h4>Methods</h4>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 ...[more]

PMID: 30377885

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Project description:BACKGROUND: Cattle and other ruminants have evolved the ability to derive most of their metabolic energy requirement from otherwise indigestible plant matter through a symbiotic relationship with plant fibre degrading microbes within a specialised fermentation chamber, the rumen. The genetic changes underlying the evolution of the ruminant lifestyle are poorly understood. The BPI-like locus encodes several putative innate immune proteins, expressed predominantly in the oral cavity and airways, which are structurally related to Bactericidal/Permeability Increasing protein (BPI). We have previously reported the expression of variant BPI-like proteins in cattle (Biochim Biophys Acta 2002, 1579, 92-100). Characterisation of the BPI-like locus in cattle would lead to a better understanding of the role of the BPI-like proteins in cattle physiology RESULTS: We have sequenced and characterised a 722 kbp segment of BTA13 containing the bovine BPI-like protein locus. Nine of the 13 contiguous BPI-like genes in the locus in cattle are orthologous to genes in the human and mouse locus, and are thought to play a role in host defence. Phylogenetic analysis indicates the remaining four genes, which we have named BSP30A, BSP30B, BSP30C and BSP30D, appear to have arisen in cattle through a series of duplications. The transcripts of the four BSP30 genes are most abundant in tissues associated with the oral cavity and airways. BSP30C transcripts are also found in the abomasum. This, as well as the ratios of non-synonymous to synonymous differences between pairs of the BSP30 genes, is consistent with at least BSP30C having acquired a distinct function from the other BSP30 proteins and from its paralog in human and mouse, parotid secretory protein (PSP). CONCLUSION: The BPI-like locus in mammals appears to have evolved rapidly through multiple gene duplication events, and is thus a hot spot for genome evolution. It is possible that BSP30 gene duplication is a characteristic feature of ruminants and that the BSP30 proteins contribute to an aspect of ruminant-specific physiology.

Dataset Information

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

Publications

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

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