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APOBコドン4311遺伝子多型は脂質代謝を変化させることによりC型肝炎ウイルスの感染性に関与する
著者
原田, 利枝 徳島大学大学院医科学教育部(医学専攻)
木村, 雅子 Tokushima University
田中, 貴大 Tokushima University
Shinomiya, Hirohiko Yoshinogawa Medical Center
本田, 浩仁 Tokushima Health Screening Center
キーワード
Hepatitis C virus
Lipid metabolism
SNPs
ApoB
資料タイプ
学位論文
抄録
Background: It has been reported that some single-nucleotide polymorphisms (SNPs) in lipid regulators such as apolipoproteins and cell surface molecules for hepatitis C virus (HCV) entry into hepatocytes are associated with HCV infection. However, it is unknown how HCV infection is affected by altered lipid metabolism resulting from the SNPs. We investigated the relationship between these SNPs and HCV infection status, and also analyzed the mechanism by which these SNPs mediate HCV infection via lipid metabolism alterations.
Methods: Serum lipid and apolipoprotein profiles were tested in 158 HCV-positive and 220 HCV-negative subjects. We selected 22 SNPs in five lipid regulator genes which were related to HCV entry into hepatocytes and to lipid metabolism (APOA1, APOB, SR-B1, LDLR, and APOE), and their polymorphisms were analyzed using the PCR-sequencespecific oligonucleotide probe-Luminex method.
Results: An APOB N4311S (g.41553a > g) SNP, rs1042034, was significantly associated with HCV positivity; the HCV positivity rate for the minor allele AA genotype was significantly higher than for genotype AG + GG (P = 0.016). Other SNPs except for APOB P2712L SNP rs676210, which is in linkage disequilibrium with rs1042034, showed no significant difference in genotype distribution. The serum level of low density lipoprotein-cholesterol (LDL-C) in the genotype AA group was significantly lower than in the genotype non-AA group (P = 0.032), whereas the triglyceride (TG) level was significantly higher (P = 0.007).
Conclusion: An APOB SNP, rs1042034, is closely associated with HCV infection through lipid metabolism alteration. The minor allele AA genotype might contribute to facilitating serum LDL uptake into hepatocytes via LDLR by modifying their affinity and interaction and may have an influence on HCV infection by their entry to the liver through the LDLR.
掲載誌名
BMC Gastroenterology
ISSN
1471230X
cat書誌ID
AA12034934
出版者
Springer Nature|BioMed Central
18
開始ページ
24
発行日
2018-01-30
備考
内容要旨・審査要旨・論文本文の公開
本論文は, 著者Rie Haradaの学位論文として提出され, 学位審査・授与の対象となっている。
権利情報
© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3198号
学位記番号
甲医第1373号
学位授与年月日
2018-05-24
学位名
博士(医学)
学位授与機関
徳島大学
部局
医学系
病院