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UMENO JUNJI Last modified date:2020.07.10

Assistant Professor / Department of Medicine and Clinical Science, Graduate School of Medical Sciences
Department of Gastroenterology
Kyushu University Hospital


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Homepage
https://kyushu-u.pure.elsevier.com/en/persons/junji-umeno
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Phone
092-642-5261
Fax
092-642-5273
Academic Degree
Impact of group IVA cytosolic phospholipase A2 gene polymorphisms on phenotypic features of patients with familial adenomatous polyposis
Field of Specialization
Gastroenterology
Research
Research Interests
  • Clinical features of chronic enteropathy associated with SLCO2A1 gene
    keyword : CEAS, small intestine, PDP
    2018.05~2028.06.
  • Clinical features of gastric neuroendocrine tumors
    keyword : neuroendocrine tumor, NET, carcinoid, ATP4A gene
    2019.06~2023.06.
  • Causative gene for familial fundic gland polyposis
    keyword : fundic gland polyposis, GAPPS
    2016.04~2019.05.
  • Causative gene for chronic nonspecific multiple ulcers of the small intestine
    keyword : chronic nonspecific multiple ulcers of the small intestine
    2012.04~2017.03.
  • clinical features of collagenous colitis
    keyword : collagenous colitis
    2012.04~2016.05.
  • ulcerative colitis related genes
    keyword : ulcerative colitis
    2012.04~2018.04.
Academic Activities
Papers
1. Junji Umeno, Tadakazu Hisamatsu, Motohiro Esaki, Atsushi Hirano, Takayuki Matsumoto, Kitazono T, A Hereditary Enteropathy Caused by Mutations in the SLCO2A1 Gene, Encoding a Prostaglandin Transporter., e1005581, 2015.11, Previously, we proposed a rare autosomal recessive inherited enteropathy characterized by persistent blood and protein loss from the small intestine as chronic nonspecific multiple ulcers of the small intestine (CNSU). By whole-exome sequencing in five Japanese patients with CNSU and one unaffected individual, we found four candidate mutations in the SLCO2A1 gene, encoding a prostaglandin transporter. The pathogenicity of the mutations was supported by segregation analysis and genotyping data in controls. By Sanger sequencing of the coding regions, 11 of 12 other CNSU patients and 2 of 603 patients with a diagnosis of Crohn’s disease were found to have homozygous or compound heterozygous SLCO2A1 mutations. In total, we identified recessive SLCO2A1 mutations located at seven sites. Using RT-PCR, we demonstrated that the identified splice-site mutations altered the RNA splicing, and introduced a premature stop codon. Tracer prostaglandin E2 uptake analysis showed that the mutant SLCO2A1 protein for each mutation exhibited impaired prostaglandin transport. Immunohistochemistry and immunofluorescence analyses revealed that SLCO2A1 protein was expressed on the cellular membrane of vascular endothelial cells in the small intestinal mucosa in control subjects, but was not detected in affected individuals. These findings indicate that loss-of-function mutations in the SLCO2A1 gene encoding a prostaglandin transporter cause the hereditary enteropathy CNSU. We suggest a more appropriate nomenclature of “chronic enteropathy associated with SLCO2A1 gene” (CEAS)..
Presentations
1. Junji Umeno, Yuta Fuyuno, Takehiro Torisu, Atsushi Hirano, Motohiro Esaki, Shunichi Yanai, Naoki Ohmiya, Tadakazu Hisamatsu, Kenji Watanabe, Naoki Hosoe, Haruhiko Ogata, Fumihito Hirai, Takashi Hisabe, Toshiyuki Matsui, Tsuneyoshi Yao, Takanari Kitazono, Takayuki Matsumoto; CEAS study group, A nationwide survey of chronic enteropathy associated with SLCO2A1 gene in Japan, The 15th Congress of European Crohn's and Colitis Organization (ECCO 2020), 2020.02, Background: Chronic enteropathy associated with SLCO2A1 gene (CEAS) is an autosomal recessive disease caused by mutations in the SLCO2A1 gene which encodes a prostaglandin transporter. It is a rare intractable disease characterized by persistent blood and protein loss due to the small intestinal ulcers. Because CEAS mimics Crohn's disease (CD) concerning ileal ulcers and stenoses, it is often difficult to distinguish CEAS from CD based on gastrointestinal findings alone. Furthermore, SLCO2A1 gene mutations are also known to cause primary hypertrophic osteoarthropathy (PHO) and some CEAS patients manifest digital clubbing, periostosis, acroosteolysis, and thickened skin as extra-intestinal manifestations. Since little is known about the clinical features of CEAS, we conducted a nationwide survey in Japan.
Methods: All study participants provided written informed consent for genetic analysis. The present study was approved by the ethics committee of each institution. During the period between 2012 and 2019, 141 patients suspected of CEAS were enrolled in this study and checked to have SLCO2A1 gene mutations. We reviewed the clinical information of genetically confirmed CEAS patients.
Results: We confirmed 61 CEAS patients (21 males and 40 females) and found 14 different types of recessive SLCO2A1 mutations. The median age at disease onset and diagnosis was 18.5 (range 1-69) and 40 (range 7-70) years, respectively. Parental consanguinity was present in 16 patients (26%). Although anaemia was present in almost all patients, only two patients experienced gross haematochezia. The median haemoglobin and serum protein levels at diagnosis were 9.7 (range 2.3-13.7) and 5.2 (2.7-8.2) g/dl, respectively. Thirty-three patients (54%) had undergone intestinal surgery. They showed relatively low inflammatory markers in blood tests (median CRP, 2.9 mg/l). The most frequently involved gastrointestinal site was ileum (93%), but the terminal ileum was rarely involved (Figure). Mild digital clubbing or periostosis was found in 16 patients (26%), with six male patients fulfilling the major diagnostic criteria of PHO. The major manifestations of PHO were more frequently found in males than in females (digital clubbing 57% vs 10%; periostosis 52% vs 11%; pachydermia 62% vs 0%).
Conclusion: Although CEAS frequently causes intestinal strictures like CD, its clinical features seem to be distinct from those of CD. Also, a gender difference in clinical symptoms needs to be considered, because concurrent PHO can be frequently seen especially in male patients with CEAS..
2. 梅野 淳嗣, 江﨑 幹宏, 平野 敦士, Clinical features of chronic enteropathy associated with SLCO2A1 gene (CEAS), 12th Congress of European Crohn's and Colitis Organisation, 2017.02.
3. 梅野 淳嗣, Chronic enteropathy associated with SLCO2A1 gene, encoding prostaglandin transporter (CEAS): relationship with primary hypertrophic osteoarthropathy. , The 4th Annual Meeting of AOCC, 2016.07.
4. Junji Umeno, Tadakazu Hisamatsu, Motohiro Esaki, Atsushi Hirano, Takayuki Matsumoto, Chronic enteropathy associated with SLCO2A1 gene, encoding prostaglandin transporter (CEAS), 2015 Advances in Inflammatory Bowel Diseases: Crohn's & Colitis Foundation of America's Clinical & Research Conference, 2015.12.