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PLOS ONE  2014 

Comparative Analysis of rs12979860 SNP of the IFNL3 Gene in Children with Hepatitis C and Ethnic Matched Controls Using 1000 Genomes Project Data

DOI: 10.1371/journal.pone.0085899

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Abstract:

The rs12979860 single nucleotide polymorphism located on chromosome 19q13.13 near the interferon L3 gene (formerly and commonly known as interleukin 28B gene) has been associated in adults with both spontaneous and treatment induced clearance of hepatitis C virus. Although the exact mechanism of these associations remains unclear, it suggests that variation in genes involved in the immune response against the virus favours viral clearance. Limited and preliminary data are available on this issue in children. The aim of the present study was to evaluate, in a representative cohort of children with perinatal infection, the potential association between rs12979860 single nucleotide polymorphism and the outcome of hepatitis C virus infection. Alleles and genotypes frequencies were evaluated in 30 children who spontaneously cleared the virus and in 147 children with persistent infection and were compared with a population sample of ethnically matched controls with unknown hepatitis C status obtained using the 1000 Genomes Project data. The C allele and the C/C genotype showed greater frequencies in the clearance group (76.7% and 56.7%, respectively) when compared with both children with viral persistence (C allele 56.5%, p = 0.004; C/C genotype 32.7%, p = 0.02) and with the ethnically matched individuals (C allele 59.7%, p = 0.02; C/C genotype 34.7%, p = 0.03). Children with the C/C genotype were 2 times more likely to clear hepatitis C virus relative to children with the C/T and T/T genotypes combined (odds ratio: 2.7; 90% confidence intervals: 1.3–5.8). The present study provides the evidence that the rs12979860 single nucleotide polymorphism influences the natural history of hepatitis C virus in children.

References

[1]  Thomas DL, Thio CL, Martin MP, Qi Y, Ge D, et al. (2009) Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature 461: 798–801.
[2]  Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, et al. (2009) Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 461: 399–401.
[3]  Urban T, Charlton MR, Goldstein DB (2012) Introduction to the genetics and biology of interleukin-28B. Hepatology 56: 361–366.
[4]  Yan KK, Guirgis M, Dinh T, George J, Dev A, et al. (2008) Treatment responses in Asians and Caucasians with chronic hepatitis C infection. World J Gastroenterol 14: 3416–3420.
[5]  Muir AJ, Bornstein JD (2004) Killenberg PG; Atlantic Coast Hepatitis Treatment Group (2004) Peginterferon alfa-2b and ribavirin for the treatment of chronic hepatitis C in blacks and non-Hispanic whites. N Engl J Med 350: 2265–2271.
[6]  Liu CH, Liu CJ, Lin CL, Liang CC, Hsu SJ, et al. (2008) Pegylated interferon-alpha-2a plus ribavirin for treatment-naive Asian patients with hepatitis C virus genotype 1 infection: a multicenter, randomized controlled trial. Clin Infect Dis 47: 1260–1269.
[7]  Ruiz-Extremera A, Mu?oz-Gámez JA, Salmerón-Ruiz MA, de Rueda PM, Quiles-Pérez R, et al. (2011) Genetic variation in interleukin 28B with respect to vertical transmission of hepatitis C virus and spontaneous clearance in HCV-infected children. Hepatology 53: 1830–1838.
[8]  Indolfi G, Sambrotta M, Moriondo M, Azzari C, Resti M (2011) Genetic variation in interleukin-28B locus is associated with spontaneous clearance of HCV in children with non-1 viral genotype infection. Hepatology 54: 1490–1491.
[9]  Bortolotti F, Verucchi G, Cammà C, Cabibbo G, Zancan L, et al. (2008) Long-term course of chronic hepatitis C in children: from viral clearance to end-stage liver disease. Gastroenterology 134: 1900–1907.
[10]  Afdhal NH (2004) The natural history of hepatitis C. Semin Liver Dis 24: 3–8.
[11]  Prendergast AJ, Klenerman P, Goulder PJ (2012) The impact of differential antiviral immunity in children and adults. Nat Rev Immunol 12: 636–648.
[12]  Genomes Project Consortium (2010) Abecasis GR, Altshuler D, Auton A, Brooks LD, Durbin RM, et al. (2010) A map of human genome variation from population-scale sequencing. Nature 467: 1061–1073.
[13]  Indolfi G, Azzari C, Resti M (2013) Perinatal Transmission of Hepatitis C Virus. J Pediatr 163: 1549–1552.
[14]  Indolfi G, Resti M (2009) Perinatal transmission of hepatitis C virus infection. J Med Virol 81: 836–843.
[15]  Resti M, Jara P, Hierro L, Azzari C, Giacchino R, et al. (2003) Clinical features and progression of perinatally acquired hepatitis C virus infection. J Med Virol 70: 373–377.
[16]  Indolfi G, Azzari C, Moriondo M, Lippi F, de Martino M, et al. (2006) Alanine transaminase levels in the year before pregnancy predict the risk of hepatitis C virus vertical transmission. J Med Virol 78: 911–914.
[17]  Novembre J, Johnson T, Bryc K, Kutalik Z, Boyko AR, et al. (2008) Genes mirror geography within Europe. Nature 456: 98–101.
[18]  Stathias V, Sotiris GR, Karagiannidis I, Bourikas G, Martinis G, et al. (2012) Exploring genomic structure differences and similarities between the Greek and European HapMap populations: implications for association studies. Ann Hum Genet 76: 472–483.
[19]  European Paediatric Hepatitis C Virus Network (2005) Three broad modalities in the natural history of vertically acquired hepatitis C virus infection. Clin Infect Dis 41: 45–51.
[20]  Langhans B, Kupfer B, Braunschweiger I, Arndt S, Schulte W, et al. (2011) Interferon-lambda serum levels in hepatitis C. J Hepatol 54: 859–865.
[21]  Naggie S, Osinusi A, Katsounas A, Lempicki R, Herrmann E, et al. (2012) Dysregulation of innate immunity in hepatitis C virus genotype 1 IL28B-unfavorable genotype patients: impaired viral kinetics and therapeutic response. Hepatology 56: 444–454.
[22]  Kollmann TR, Crabtree J, Rein-Weston A, Blimkie D, Thommai F, et al. (2009) Neonatal innate TLR-mediated responses are distinct from those of adults. J Immunol 183: 7150–7160.

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