Kayoko Sato

Nagasaki University Hospital, Nagasaki, Nagasaki, Japan

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Publications (3)10.54 Total impact

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    ABSTRACT: 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. 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. 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). 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.
    Journal of Clinical Immunology 09/2009; 29(6):815-25. · 3.38 Impact Factor
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    ABSTRACT: To identify genetic determinants of inflammatory bowel disease (IBD), we examined an association between polymorphisms of both the programmed cell death 1 gene (PDCD1) and the src homology 2 domain-containing tyrosine phosphatase 2 gene (PTPN11) and susceptibility to IBD. Study subjects comprised 114 patients with ulcerative colitis (UC), 83 patients with Crohn's disease, and 200 healthy control subjects. Five single nucleotide polymorphisms (SNPs) in PDCD1 and PTPN11 were detected by polymerase chain reaction restriction fragment length polymorphism. Subsequently, haplotypes composed of the two SNPs in PTPN11 were constructed. The frequencies of the Hap 1 haplotype and its homozygous 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. 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.
    Journal of Clinical Immunology 02/2009; 29(3):303-10. · 3.38 Impact Factor
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    ABSTRACT: Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a chronic inflammatory disorder characterized by intractable inflammation specific to the gastrointestinal tract. The precise etiology of IBD remains unknown. Recently, haplotypes of peptidylarginine deiminase type 4 (PADI4) have been identified as the rheumatoid arthritis (RA)-susceptible gene. PADI4 is located at 1p36, which is one of chromosomal loci susceptible for IBD. Then, we examined whether haplotypes and diplotypes of PADI4 are associated with IBD in the Japanese population. We studied haplotypes of PADI4 in 114 patients with UC, 83 patients with CD, and 200 gender-matched healthy controls by PCR-restriction fragment length polymorphism. Frequencies and distributions of haplotypes and diplotypes were compared statistically between patients and controls by logistic regression analysis. The frequency of haplotype 1 was significantly decreased in patients with UC, compared to that in controls (P=0.037; odds ratio (OR)=0.702). In contrast, the frequency of haplotype 2 in patients with UC was significantly higher than that in controls (P=0.003; OR=1.722). Moreover, of a total of 114 patients with UC, 15 (13.2%) had a diplotype homozygous for haplotype 2, the frequency being significantly higher than in controls (9/200, 4.5%; P=0.008, OR=3.215). Our results indicate that haplotype 1 of PADI4 is associated with non-susceptibility to UC, whereas haplotype 2 is susceptible to UC. Thus, it is likely that PADI4 is one of genetic determinants of UC in the Japanese population.
    Clinical Immunology 03/2008; 126(2):165-71. · 3.77 Impact Factor