Harada, Rie Tokushima University
Kimura, Masako Tokushima University
Sato, Yasushi Tokushima University Tokushima University Educator and Researcher Directory
Taniguchi, Tatsuya Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Tomonari, Tetsu Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Tanaka, Takahiro Tokushima University
Tanaka, Hironori Tokushima University Tokushima University Educator and Researcher Directory
Muguruma, Naoki Tokushima University KAKEN Search Researchers
Shinomiya, Hirohiko Yoshinogawa Medical Center
Honda, Hirohito Tokushima Health Screening Center
Imoto, Issei Tokushima University KAKEN Search Researchers
Sogabe, Masahiro Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Okahisa, Toshiya Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Hepatitis C virus
Thesis or Dissertation
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.
Springer Nature|BioMed Central
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。
© 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.
|DOI (Published Version)|
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k3198_abstract_review.pdf 1.57 MB
k3198_fulltext.pdf 379 KB
|MEXT report number||
Doctor of Medical Science