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ID 111808
Title Alternative
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
Author
Harada, Rie Tokushima University
Kimura, Masako Tokushima University
Tanaka, Hironori Tokushima University
Shinomiya, Hirohiko Yoshinogawa Medical Center
Honda, Hirohito Tokushima Health Screening Center
Keywords
Hepatitis C virus
Lipid metabolism
SNPs
ApoB
Content Type
Thesis or Dissertation
Description
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.
Journal Title
BMC Gastroenterology
ISSN
1471230X
NCID
AA12034934
Publisher
Springer Nature|BioMed Central
Volume
18
Start Page
24
Published Date
2018-01-30
Remark
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。
Rights
© 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.
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3198号
Diploma Number
甲医第1373号
Granted Date
2018-05-24
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
Medical Sciences
University Hospital