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

Area of Science:

• Pharmacogenomics
• Gastroenterology
• Genetics

Background:

• Individual responses to nonsteroidal anti-inflammatory drugs (NSAIDs) vary significantly, particularly concerning NSAID-induced enteropathy.
• Understanding the genetic factors influencing this variability is crucial for personalized medicine.

Purpose of the Study:

• To identify specific single nucleotide polymorphisms (SNPs) strongly associated with NSAID-induced enteropathy.
• To investigate the role of the bactericidal/permeability-increasing fold-containing family B member 4 (BPIFB4) gene in NSAID-induced small intestinal damage.

Main Methods:

• Genome-wide association study (GWAS) and genotype imputation were performed on 150 subjects with documented NSAID-induced small intestinal damage.
• Subjects were grouped based on NSAID treatment (loxoprofen or celecoxib) and the severity of small intestinal mucosal breaks.

Main Results:

• Five SNPs within the BPIFB4 gene exhibited the strongest association with NSAID-induced enteropathy (lowest p-value: 2.69 × 10⁻⁷).
• Notably, rs2070325 (V268I) was among the identified nonsynonymous SNPs in BPIFB4.
• Genotype imputation identified an additional 23 suggestive SNPs in BPIFB4.

Conclusions:

• Single nucleotide polymorphisms (SNPs) in the BPIFB4 gene are significantly associated with NSAID-induced small intestinal mucosal injury.
• These findings highlight BPIFB4 as a potential genetic marker for predicting susceptibility to NSAID-induced enteropathy.