BMC Gastroenterology (Jan 2018)

APOB codon 4311 polymorphism is associated with hepatitis C virus infection through altered lipid metabolism

  • Rie Harada,
  • Masako Kimura,
  • Yasushi Sato,
  • Tatsuya Taniguchi,
  • Tetsu Tomonari,
  • Takahiro Tanaka,
  • Hironori Tanaka,
  • Naoki Muguruma,
  • Hirohiko Shinomiya,
  • Hirohito Honda,
  • Issei Imoto,
  • Masahiro Sogabe,
  • Toshiya Okahisa,
  • Tetsuji Takayama

DOI
https://doi.org/10.1186/s12876-018-0747-5
Journal volume & issue
Vol. 18, no. 1
pp. 1 – 8

Abstract

Read online

Abstract 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-sequence-specific 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.

Keywords