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Association of low-density lipoprotein receptor genotypes with hepatitis C viral load

Genes & Immunity volume 15, pages 16–24 (2014)Cite this article

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Abstract

Several data suggest that low-density lipoprotein receptor (LDLR) is a co-receptor for hepatitis C virus (HCV). Soluble LDLR can inhibit HCV infectivity; greater plasma low-density lipoprotein levels are associated with treatment success; LDLR genotypes have a synergistic impact on the likelihood of achieving SVR with Peg-IFN plus RBV, as well as on viral kinetics after starting treatment. The objective of this study was to assess the impact of genetic polymorphisms in genes related to cholesterol synthesis and transport pathways on pre-treatment plasma HCV viral load (VL). A total of 442 patients infected with HCV and treatment naive were prospectively recruited. One hundred forty-four SNPs located in 40 genes from the cholesterol synthesis/transport and IL28B were genotyped and analyzed for genetic association with pre-treatment plasma HCV VL. SNPs rs1433099 and rs2569540 of LDLR showed association with plasma HCV VL (P=4 × 10−4 and P=2 × 10−3) in patients infected with genotypes 1 and 4. A haplotype including the last three exons of LDLR showed association with the cutoff level of 600 000 IU ml−1 VL for genotypes 1 and 4 (OR=0.27; P=8 × 10−6), as well as a quantitative VL (mean±s.d.: 6.19±0.9 vs CC+CG 5.58±1.1 logIU ml−1, P=8 × 10−5). LDLR genotypes are a major genetic factor influencing HCV VL in patients infected with genotypes 1 and 4.

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Acknowledgements

This study has been supported in part by grants from the Spanish Health Ministry (ISCIII-RETIC RD06/006 and projects PI10/01664 and PI10/01232) from the Consejería de Salud de la Junta de Andalucía (PI-0247-2010) and from the Fundación para la Investigación y la Prevención del Sida en España (reference 360799/09). JAP is the recipient of an extension grant from the Instituto de Salud Carlos III (grant number Programa-I3SNS). KN is the recipient of a ‘Sara Borrell’ postdoctoral perfection grant from the Instituto de Salud Carlos III (SCO/523/2008).

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Authors and Affiliations

  1. Department of Experimental, Immunogenetics Unit, Biology Faculty of Sciences, Universidad de Jaén, Jaén, Spain

    A Caruz & R Herrero

  2. Unit of Infectious Diseases and Microbiology, Hospital Universitario de Valme, Instituto de Biomedicina de Sevilla (IBiS), Seville, Spain

    K Neukam, L M Real & J A Pineda

  3. Unit of Infectious Diseases, Maimonides Institute for Biomedical Research (IMIBIC), Hospital Universitario Reina Sofía, Córdoba, Spain

    A Rivero-Juárez, Á Camacho & A Rivero

  4. Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain

    P Barreiro & P Labarga

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  1. A Caruz
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Correspondence to J A Pineda.

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Caruz, A., Neukam, K., Rivero-Juárez, A. et al. Association of low-density lipoprotein receptor genotypes with hepatitis C viral load. Genes Immun 15, 16–24 (2014). https://doi.org/10.1038/gene.2013.56

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