Genetic polymorphism in ATG16L1 gene influences the response to adalimumab in Crohn's disease patients

Pharmacogenomics. 2015;16(3):191-204. doi: 10.2217/pgs.14.172.

Abstract

Aim: To see if SNPs could help predict response to biological therapy using adalimumab (ADA) in Crohn's disease (CD).

Materials & methods: IBDQ index and CRP levels were used to monitor therapy response. We genotyped 31 CD-associated genes in 102 Slovenian CD patients.

Results: The strongest association for treatment response defined as decrease in CRP levels was found for ATG16L1 SNP rs10210302. Additional SNPs in 7 out of 31 tested CD-associated genes (PTGER4, CASP9, IL27, C11orf30, CCNY, IL13, NR1I2) showed suggestive association with ADA response.

Conclusion: Our results suggest ADA response in CD patients is genetically predisposed by SNPs in CD risk genes and suggest ATG16L1 as most promising candidate gene for drug response in ADA treatment. Original submitted 24 September 2014; Revision submitted 1 December 2014.

Keywords: Crohn's disease; adalimumab; biological drugs; pharmacogenomics; single nucleotide polymorphism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab / therapeutic use*
  • Adult
  • Autophagy-Related Proteins
  • C-Reactive Protein / metabolism
  • Carrier Proteins / genetics*
  • Crohn Disease / genetics*
  • Crohn Disease / therapy*
  • Female
  • Genetic Association Studies
  • Genetic Markers
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Slovenia
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors

Substances

  • ATG16L1 protein, human
  • Autophagy-Related Proteins
  • Carrier Proteins
  • Genetic Markers
  • Tumor Necrosis Factor-alpha
  • C-Reactive Protein
  • Adalimumab