title: Strong evidence of a combination polymorphism of the tyrosine kinase 2 gene and the signal transducer and activator of transcription 3 gene as a DNA-based biomarker for susceptibility to Crohn's disease in the Japanese population.
abstract: OBJECTIVE
  An association between susceptibility to inflammatory bowel disease (IBD) and polymorphisms of both the tyrosine kinase 2 gene (TYK2) and the signal transducer and activator of transcription 3 gene (STAT3) was examined in a Japanese population in order to identify the genetic determinants of IBD.
  
  
  METHODS
  The study subjects comprised 112 patients with ulcerative colitis, 83 patients with Crohn's disease (CD), and 200 healthy control subjects. Seven tag single-nucleotide polymorphisms (SNPs) in TYK2 and STAT3 were detected by PCR-restriction fragment length polymorphism.
  
  
  RESULTS
  The frequencies of a C allele and its homozygous C/C genotype at rs2293152 SNP in STAT3 in CD patients were significantly higher than those in control subjects (P = 0.007 and P = 0.001, respectively). Furthermore, out of four haplotypes composed of the two tag SNPs (rs280519 and rs2304256) in TYK2, the frequencies of a Hap 1 haplotype and its homozygous Hap 1/Hap1 diplotype were significantly higher in CD patients in comparison to those in control subjects (P = 0.023 and P = 0.024, respectively). In addition, the presence of both the C/C genotype at rs2293152 SNP in STAT3 and the Hap 1/Hap 1 diplotype of TYK2 independently contributes to the pathogenesis of CD and significantly increases the odds ratio to 7.486 for CD (P = 0.0008).
  
  
  CONCLUSIONS
  TYK2 and STAT3 are genetic determinants of CD in the Japanese population. This combination polymorphism may be useful as a new genetic biomarker for the identification of high-risk individuals susceptible to CD.
authors: Department of Pharmacotherapeutics, Nagasaki University Graduate School of Biomedical Sciences, Bunkyo-machi, Nagasaki, Japan.
authors: Kayoko
authors: K
authors: Sato
authors: Mizuho
authors: M
authors: Shiota
authors: Sayaka
authors: S
authors: Fukuda
authors: Eiko
authors: E
authors: Iwamoto
authors: Haruhisa
authors: H
authors: Machida
authors: Tatsuo
authors: T
authors: Inamine
authors: Shinji
authors: S
authors: Kondo
authors: Katsunori
authors: K
authors: Yanagihara
authors: Hajime
authors: H
authors: Isomoto
authors: Yohei
authors: Y
authors: Mizuta
authors: Shigeru
authors: S
authors: Kohno
authors: Kazuhiro
authors: K
authors: Tsukamoto
mesh_terms: D016022:Case-Control Studies; D003424:Crohn Disease / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D007564:Japan / Q000453:epidemiology; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D050796:STAT3 Transcription Factor / Q000235:genetics*; D053634:TYK2 Kinase / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D053634:TYK2 Kinase