2021 Fiscal Year Final Research Report
Therapeutic strategy for reactivation of drug-resistant cytomegalovirus strain in ulcerative colitis by genomic analysis
| Project/Area Number |
19K08466
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
Osawa Satoshi 浜松医科大学, 医学部附属病院, 講師 (10397391)
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| Co-Investigator(Kenkyū-buntansha) |
杉本 健 浜松医科大学, 医学部, 教授 (20529507)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 薬剤耐性サイトメガロウイルス / 潰瘍性大腸炎 / ガンシクロビル / UL97遺伝子 / サイトメガロウイルス腸炎 / ゲノム解析 |
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| Outline of Final Research Achievements |
Cytomegalovirus (CMV) reactivation in the colon is common in patients with severe ulcerative colitis (UC). Ganciclovir (GCV) resistance conferring CMV UL97 gene mutations have been reported. In this study, we investigated the prevalence of CMV UL97 gene mutations in patients with colonic CMV infection associated with or without UC. Twenty-two GCV-naive patients with colonic CMV infection, 15 with UC and 7 with other diseases, were enrolled. Frozen biopsy samples or formalin-fixed paraffin-embedded samples were used for sanger DNA sequencing. Polymorphisms were frequently detected in codons N68D (100%), I244V (100%), and D605E (86.4%). However, no known GCV resistance mutations were found. There was no difference between the ratio of polymorphisms in patients with and without UC. In conclusions, we did not detect UL97 gene mutations associated with GCV resistance in GCV-naive patients with or without UC. D605E polymorphism may be used as a genetic marker for CMV in East Asian countries.
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| Free Research Field |
消化器内科学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究から、潰瘍性大腸炎患者におけるサイトメガロウイルス(CMV)感染におけるガンシクロビル（GCV))耐性に関与するUL97遺伝子変異頻度の実態が非潰瘍性大腸炎患者との比較とともに明らかとなった。日常診療では抗ウイルス薬治療として一律にGCVが選択されているが、GCV-naive症例でのUL97遺伝子変異は極めて少ないことから、妥当であると考えられた。D605E変異は過去の報告と同様で日本人で高率であり、東アジア人に多くみられる遺伝子多型と考えられた。今後はGCV治療抵抗症例でのUL97遺伝子変異同定が、抗ウイルス薬選択のオーダーメイド化のため、さらなる検討課題である。
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