Polymorphism of Receptor-Type Tyrosine-Protein Phosphatase Delta gene is associated with the development and progression of non-alcoholic fatty liver disease. 33 1
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- Material Type
- 博士論文
- ISSN
- 0815-9319
- Volume
- 33 1
- Author/Editor
- 中嶋, 駿介
- Publication Date
- 2018-01
- Publication Date (W3CDTF)
- 2018-01
- Periodical title
- Journal of gastroenterology and hepatology
- Degree Grantor
- 旭川医科大学
- Date Granted
- 2017-09-29
- Date Granted (W3CDTF)
- 2017-09-29
- Dissertation Number
- 甲第519号
- Degree Type
- 博士（医学）
- Conferring No. (Dissertation)
- 甲第519号
- Text Language Code
- eng
- Subject Heading
- Note (General)
- BACKGROUND AND AIM: Some single-nucleotide polymorphisms (SNPs) are associated with the development of non-alcoholic fatty liver disease (NAFLD). As one of the genetic factors, PNPLA3 rs738409 (I148M) is important to associate with pathogenesis of NAFLD. Because other SNPs remain unclear in Japan, we performed a high-throughput sequencing that targeted more than 1000 genes to identify a novel genetic variant in Japanese patients with NAFLD. METHODS: The present study in 36 NAFLD patients and 27 healthy volunteers was performed. A high-throughput sequencer was used to detect the gene variations. Candidate genes were validated by TaqMan SNP genotyping assay in 53 NAFLD patients and 41 healthy volunteers. To investigate the function of candidate gene, we performed biochemical analyses in cultured hepatocytes and liver tissues. RESULTS: EXO1 rs1047840, PTPRD rs35929428, IFNAR2 rs2229207, CPOX rs1131857, IL23R rs1884444, IL10RA rs2228055, and FAM3B rs111988437 were identified as candidate genetic variants, and PTPRD rs35929428 was only extracted as a SNP predicting to cause protein dysfunction. In validation analysis, PTPRD rs35929428 associated with the development of NAFLD (P = 0.015, odds ratio = 5.00, 95% confidence interval: 1.33-18.70). In addition, PTPRD rs35929428 was associated with Fib-4 index and with hepatic fat droplets. Biochemical analyses indicated that PTPRD rs35929428 promoted dephosphorylation of tyrosine 705 signal transducer and activator of transcription 3 (Tyr 705) in hepatocytes. CONCLUSION: PTPRD rs35929428 was a novel SNP in patients with NAFLD. Through exacerbation of the dephosphorylation of signal transducer and activator of transcription 3 (Tyr 705) in hepatocytes, PTPRD rs35929428 might play a role in hepatic lipid accumulation and fibrosis, followed by the development of NAFLD.identifier:PMID：28497593開始ページ : 283終了ページ : 290
- DOI
- info:doi/10.1111/jgh.13820
- Persistent ID (NDL)
- info:ndljp/pid/11378577
- Collection
- Collection (Materials For Handicapped People:1)
- Collection (particular)
- 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文
- Acquisition Basis
- 博士論文（自動収集）
- Date Accepted (W3CDTF)
- 2019-11-04T14:30:53+09:00
- Format (IMT)
- application/pdf
- Access Restrictions
- 国立国会図書館内限定公開
- Service for the Digitized Contents Transmission Service
- 図書館・個人送信対象外
- Availability of remote photoduplication service
- 可
- Periodical Title (URI)
- Data Provider (Database)
- 国立国会図書館 : 国立国会図書館デジタルコレクション