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). Conclusion 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.

Objective To identify genetic determinants of inflammatory bowel disease (IBD), we examined an association between polymorphisms of both the Subsequently, haplotypes composed of the two SNPs in PTPN11 were constructed. Results The frequencies of the Hap 1 haplotype and itsNarumi et al. 5homozygous Hap 1/Hap 1 diplotype of PTPN11 were significantly increased in UC patients compared to control subjects (P = 0.011 and P = 0.030, respectively). While, no association was found for PDCD1 for UC or CD and none for PTPN11 for CD.Conclusion PTPN11 is a genetic determinant for the pathogenesis of UC, and haplotyping of PTPN11 may be useful as a genetic biomarker to identify high-risk individuals susceptible to UC.