title: Genetic Polymorphisms of IL-17F and TRAF3IP2 Could Be Predictive Factors of the Long-Term Effect of Infliximab against Crohn's Disease.
abstract: BACKGROUND
  We aimed to identify certain genes related to response to infliximab (IFX) and biomarkers to predict the IFX effect for Japanese Crohn's disease (CD) patients by performing an association study of single nucleotide polymorphisms (SNPs) in candidate genes in the interleukin- (IL-) 17 signaling pathway with response to IFX after 1 year of treatment.
  
  
  METHODS
  A total of 103 patients were divided into two groups, responders and nonresponders. Twenty-eight tag SNPs in 5 genes were genotyped. The frequencies of alleles and genotypes of each SNP were compared between responders and nonresponders in three different inheritance models. A genetic test was performed using a combination of the associated SNPs as biomarkers.
  
  
  RESULTS
  Multivariate logistic regression analysis indicated that the four variable factors, concomitant use of immunomodulators, penetrating disease, a G/G genotype of rs766748 in IL-17F, and a C/C or C/A genotype of rs1883136 in TRAF3IP2, independently contributed to response to IFX after 1 year of treatment. Genetic test using the polymorphisms of these genes perfectly predicted the responder and nonresponder CD patients with both concomitant use of immunomodulators and penetrating disease.
  
  
  CONCLUSIONS
  IL17F and TRAF3IP2 are one of IFX-related genes, useful as biomarkers of IFX response, and may be target molecules for new therapeutic drugs.
authors.affiliation: Department of Gastroenterology and Hepatology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Urabe
authors.affiliation: Department of Gastroenterology and Hepatology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Isomoto
authors.affiliation: Department of Gastroenterology, Oita Red Cross Hospital, 3-2-27 Chiyo-machi, Oita 870-0033, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ishida
authors.affiliation: Department of Pharmacotherapeutics, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Maeda
authors.affiliation: Department of Pharmacotherapeutics, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Inamine
authors.affiliation: Department of Pharmacotherapeutics, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kondo
authors.affiliation: Department of Hospital Pharmacy, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: Norihide
authors.initials: N
authors.lastname: Higuchi
authors.affiliation: Department of Hospital Pharmacy, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Sato
authors.affiliation: Department of Gastroenterology and Hepatology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: Ryohei
authors.initials: R
authors.lastname: Uehara
authors.affiliation: Department of Gastroenterology and Hepatology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yajima
authors.affiliation: Department of Gastroenterology and Hepatology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: Haruhisa
authors.initials: H
authors.lastname: Machida
authors.affiliation: Department of Gastroenterology and Hepatology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: Chun Chuan
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology and Hepatology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fukuda
authors.affiliation: Department of Gastroenterology and Hepatology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: Fuminao
authors.initials: F
authors.lastname: Takeshima
authors.affiliation: Department of Gastroenterology and Hepatology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakao
authors.affiliation: Department of Pharmacotherapeutics, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tsukamoto
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000483:Alleles; D015415:Biomarkers / Q000378:metabolism; D003424:Crohn Disease / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use; D005838:Genotype; D006801:Humans; D000069285:Infliximab / Q000627:therapeutic use*; D020381:Interleukin-17 / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D005765:Gastrointestinal Agents; C440021:IL17F protein, human; D020381:Interleukin-17; C414202:TRAF3IP2 protein, human; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D000069285:Infliximab