東北大学 · 医学
Yoichi Kakuta教授の研究室は、炎症性腸疾患（IBD）の発症メカニズムと個別化医療の実現を目指して、日本人集団に特有の遺伝的要因や薬物代謝異常の解明を主な研究テーマとしています。特にチオプリン系薬剤の副作用メカニズムや、日本人に特有のCD感受性遺伝子（例：RAP1A）の同定、およびアレルギー反応の遺伝的素因の解明に注力しています。また、パナセア細胞の形態と関連する遺伝子変異の解析を通じて、自己飲食物関連の自己免疫制御機構の解明も進めています。
Figures are computed from collected data and may differ slightly.
The thiopurine drugs 6-mercaptopurine (6-MP) and azathiopurine (AZA) are widely used to treat inflammatory bowel disease. However, the incidence of adverse reactions is high, particularly in Asia, and the mechanisms of toxicity in Asian populations remain unclear. Thiopurine S-methyltransferase (TPMT) is a well-known enzyme that inactivates AZA or 6-MP through methylation and is one of the few pharmacogenetic predictors used in clinical settings in Western countries. Individuals carrying TPMT-de
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<b>BACKGROUND.</b> Morphological patterns of Paneth cells are a prognostic biomarker in Western Crohn's disease (CD) patients, and are associated with autophagy-associated <i>ATG16L1</i> and <i>NOD2</i> variants. We hypothesized that genetic determinants of Paneth cell phenotype in other ethnic CD cohorts are distinct but also involved in autophagy. <b>METHODS.</b> We performed a hypothesis-driven analysis of 56 single nucleotide polymorphisms (SNPs) associated with CD susceptibility or known to
TNFSF15 is a susceptibility gene for Crohn's disease (CD). It remains to be elucidated how the associated single nucleotide polymorphisms (SNPs) in TNFSF15 affect the susceptibility to CD. Because there are no non-synonymous SNPs in TNFSF15, we speculated that one or more of the SNPs associated with CD may act as cis-regulatory SNPs. To reveal the effects of the SNPs on the transcriptional activity of TNFSF15, we first examined the allelic expression imbalance of TNFSF15 in peripheral blood mono
RAP1A is a novel susceptibility locus for CD in the Japanese population.
Mesalamine allergy was more common in ulcerative colitis than in Crohn's disease. We identified a novel genetic association with and developed a combined clinical/genetic model for this adverse event.
IL23R p.G149R is a susceptibility locus for UC in Japanese individuals. The GG genotype of rs117506082 at HLA loci may predict a better clinical course.
We confirmed the existence of cis-regulated ASM around IBD susceptibility genes and the association between ASM SNP (rs36221701) genotype and SMAD3 expression, a susceptibility gene for IBD. These results give us supporting evidence that DNA methylation mediates genetic effects on disease susceptibility.
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