Tohoku University · 의학
Yoichi Kakuta 교수의 연구실은 장내 염증성 질환, 특히 크론병과 궤양성 대장염의 유전적 기반과 약물 유전체학을 중심으로 연구를 진행하고 있습니다. 아시아계 환자, 특히 일본인 환자에서의 약물 부작용 메커니즘과 유전적 소인을 규명하며, TPMT, RAP1A, TNFSF15 등 유전자 변이와 Paneth 세포 기능, 면역 조절 경로의 상관관계를 탐구하고 있습니다. 특히 약물 대사 효소, 자가포식과 관련된 유전자, 그리고 면역 조절 유전자 기반의 개인 맞춤 치료 전략 개발에 초점을 맞추고 있습니다.
표시된 성과는 수집된 데이터 기준으로 산출되며, 일부 차이가 있을 수 있습니다.
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
a decrease in NO production.
<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.
