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Pleiotropy and allelic heterogeneity in the TOMM40-APOE genomic region related to clinical and metabolic features of hepatitis C infection.

Publication ,  Journal Article
Chiba-Falek, O; Linnertz, C; Guyton, J; Gardner, SD; Roses, AD; McCarthy, JJ; Patel, K
Published in: Hum Genet
December 2012

Hepatitis C virus (HCV) modulates host lipid metabolism as part of its lifecycle and is dependent upon VLDL for co-assembly and secretion. HCV dyslipidemia is associated with steatosis, insulin resistance, IL28B genotype and disease progression. Apolipoprotein E (ApoE) is an important lipid transport protein, a key constituent of VLDL, and is involved in immunomodulation. Our aims were to determine the role of APOE regional polymorphisms on host lipids, IL28B genotype and disease severity in chronic HCV (CHC) patients. The study cohort included 732 CHC patients with available DNA for genotype determination of four polymorphisms in the chromosome 19 region that encompasses the TOMM40, APOE and APOC1 genes. Serum lipid analysis and apolipoproteins levels were measured using an immunoturbidimetric assay. APOE rs7412 polymorphism (capturing the ε2 isoform) was significantly associated with serum ApoE levels in both Caucasians and African-American patients (p = 2.3 × 10(-11)) and explained 7 % of variance in serum ApoE. Among IL28B-CC patients (n = 196), the rs429358 (defines ε4 isoform) and TOMM40 '523' S polymorphisms were associated with 12 % of variance in ApoB levels. Patients homozygous for the APOE ε3 isoform had a greater than twofold increased odds of F2-F4 fibrosis (p = 1.8 × 10(-5)), independent of serum lipid and lipoprotein levels. There were no associations between APOE polymorphisms and serum HDL-C, APO-CIII and triglycerides. In CHC patients, genetic heterogeneity in the APOE/TOMM40 genomic region is significantly associated with variation in serum ApoE and ApoB levels, and also with fibrosis suggesting a pleiotropic attribute of this genomic region.

Duke Scholars

Published In

Hum Genet

DOI

EISSN

1432-1203

Publication Date

December 2012

Volume

131

Issue

12

Start / End Page

1911 / 1920

Location

Germany

Related Subject Headings

  • White People
  • Polymorphism, Single Nucleotide
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Middle Aged
  • Membrane Transport Proteins
  • Male
  • Liver Cirrhosis
  • Interleukins
  • Interferons
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Chiba-Falek, O., Linnertz, C., Guyton, J., Gardner, S. D., Roses, A. D., McCarthy, J. J., & Patel, K. (2012). Pleiotropy and allelic heterogeneity in the TOMM40-APOE genomic region related to clinical and metabolic features of hepatitis C infection. Hum Genet, 131(12), 1911–1920. https://doi.org/10.1007/s00439-012-1220-0
Chiba-Falek, Ornit, Colton Linnertz, John Guyton, Stephen D. Gardner, Allen D. Roses, Jeanette J. McCarthy, and Keyur Patel. “Pleiotropy and allelic heterogeneity in the TOMM40-APOE genomic region related to clinical and metabolic features of hepatitis C infection.Hum Genet 131, no. 12 (December 2012): 1911–20. https://doi.org/10.1007/s00439-012-1220-0.
Chiba-Falek O, Linnertz C, Guyton J, Gardner SD, Roses AD, McCarthy JJ, et al. Pleiotropy and allelic heterogeneity in the TOMM40-APOE genomic region related to clinical and metabolic features of hepatitis C infection. Hum Genet. 2012 Dec;131(12):1911–20.
Chiba-Falek, Ornit, et al. “Pleiotropy and allelic heterogeneity in the TOMM40-APOE genomic region related to clinical and metabolic features of hepatitis C infection.Hum Genet, vol. 131, no. 12, Dec. 2012, pp. 1911–20. Pubmed, doi:10.1007/s00439-012-1220-0.
Chiba-Falek O, Linnertz C, Guyton J, Gardner SD, Roses AD, McCarthy JJ, Patel K. Pleiotropy and allelic heterogeneity in the TOMM40-APOE genomic region related to clinical and metabolic features of hepatitis C infection. Hum Genet. 2012 Dec;131(12):1911–1920.
Journal cover image

Published In

Hum Genet

DOI

EISSN

1432-1203

Publication Date

December 2012

Volume

131

Issue

12

Start / End Page

1911 / 1920

Location

Germany

Related Subject Headings

  • White People
  • Polymorphism, Single Nucleotide
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Middle Aged
  • Membrane Transport Proteins
  • Male
  • Liver Cirrhosis
  • Interleukins
  • Interferons
  • Humans