Literature DB >> 24259970

Interleukin 28B-related polymorphisms: a pathway for understanding hepatitis C virus infection?

Raquel Francine Liermann Garcia1, Simone Moreira, Ana Lucia de Araújo Ramos, Leslie Ecker Ferreira, Angelo Alves de Mattos, Cristiane Valle Tovo, Lysandro Alsina Nader, Juliene Antonio Ramos, Edson Rondinelli, Arnaldo de Jesus Dominici, Christian Evangelista Garcia, Mauro de Souza Leite Pinho, Carlos Eduardo Brandão-Mello, Cristiane Alves Villela-Nogueira, Paulo Henrique Condeixa de França.   

Abstract

AIM: To analyze the role of rs12979860 and rs8099917 polymorphisms in hepatitis C virus (HCV) genotype 1 infection of Brazilians.
METHODS: A total of 145 adult patients diagnosed with genotype 1 chronic hepatitis C (CHC) who had completed a 48-wk regimen of pegylated-interferon α-2a or -2b plus ribavirin combination therapy were recruited from six large urban healthcare centers and 199 healthy blood donors (controls) from a single site between January 2010 and January 2012. Data on the patients' response to treatment was collected. Polymerase chain reaction-restriction fragment length polymorphism genotyping of the interleukin (IL)28B gene fragment encompassing the single nucleotide polymorphisms (SNPs) rs12979860 (C/T) and rs8099917 (T/G) was carried out for 79 of the CHC patients and 199 of the controls. Bi-directional amplicon sequencing of the two SNPs was carried out for the remaining 66 CHC patients.
RESULTS: SNP rs12979860 genotyping was successful in 99.5% of the controls and 97.2% of the CHC patients, whereas the SNP rs8099917 genotyping was successful in 95.5% of the controls and 100% of the CHC patients. The genotype and allele distributions for both rs12979860 and rs8099917 were significantly different between the control and CHC patient groups, with significantly higher genotype frequencies of CC and TT in the controls (P = 0.037 and 0.046, respectively) and of TT and GG in the CHC patients (P = 0.0009 and 0.0001, respectively). Analysis of the CHC patients who achieved sustained virological response (SVR) to treatment (n = 55) indicated that the rs12979860 C allele and CC genotype were predictors of SVR (P = 0.02). No significant correlation was found between rs8099917 genotypes and treatment response, but carriers of the T allele showed significantly higher rates of SVR (P = 0.02). Linkage disequilibrium analysis of the group that achieved SVR showed a significant association between rs12979860 and rs8099917 (P = 0.07).
CONCLUSION: The higher allele frequency of rs12979860 C and rs8099917 T observed in non-HCV-infected individuals may indicate a potential protective role for these IL28B-related polymorphisms.

Entities:  

Keywords:  Brazil; Hepatitis C; Interleukin 28B; Single nucleotide polymorphisms; Sustained virological response

Mesh:

Substances:

Year:  2013        PMID: 24259970      PMCID: PMC3831221          DOI: 10.3748/wjg.v19.i42.7399

Source DB:  PubMed          Journal:  World J Gastroenterol        ISSN: 1007-9327            Impact factor:   5.742


  22 in total

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5.  Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: a genome-wide association study.

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Journal:  Nat Genet       Date:  2009-09-13       Impact factor: 38.330

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Journal:  Nat Genet       Date:  2009-09-13       Impact factor: 38.330

10.  Genetic variation in IL28B and spontaneous clearance of hepatitis C virus.

Authors:  David L Thomas; Chloe L Thio; Maureen P Martin; Ying Qi; Dongliang Ge; Colm O'Huigin; Judith Kidd; Kenneth Kidd; Salim I Khakoo; Graeme Alexander; James J Goedert; Gregory D Kirk; Sharyne M Donfield; Hugo R Rosen; Leslie H Tobler; Michael P Busch; John G McHutchison; David B Goldstein; Mary Carrington
Journal:  Nature       Date:  2009-10-08       Impact factor: 49.962

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  2 in total

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  2 in total

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