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.
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.
Sato
Kayoko
K
Department of Pharmacotherapeutics, Nagasaki University Graduate School of Biomedical Sciences, Bunkyo-machi, Nagasaki, Japan.
Shiota
Mizuho
M
Fukuda
Sayaka
S
Iwamoto
Eiko
E
Machida
Haruhisa
H
Inamine
Tatsuo
T
Kondo
Shinji
S
Yanagihara
Katsunori
K
Isomoto
Hajime
H
Mizuta
Yohei
Y
Kohno
Shigeru
S
Tsukamoto
Kazuhiro
K
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*
D005819:Genetic Markers; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D053634:TYK2 Kinase