Brief Article
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World J Gastroenterol. Nov 14, 2013; 19(42): 7399-7404
Published online Nov 14, 2013. doi: 10.3748/wjg.v19.i42.7399
Interleukin 28B-related polymorphisms: A pathway for understanding hepatitis C virus infection?
Raquel Francine Liermann Garcia, 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
Raquel Francine Liermann Garcia, Simone Moreira, Leslie Ecker Ferreira, Christian Evangelista Garcia, Mauro de Souza Leite Pinho, Paulo Henrique Condeixa de França, Departamento de Medicina, Universidade da Região de Joinville/Univille, Joinville, 89219-719 Santa Catarina, Brazil
Raquel Francine Liermann Garcia, Christian Evangelista Garcia, Departamento de Clinica Médica e Cirurgia Geral Hospital Municipal São José, Joinville, 89202-000 Santa Catarina, Brazil
Ana Lucia de Araújo Ramos, Cristiane Alves Villela-Nogueira, Departamento de Clínica Médica, Serviço de Hepatologia, Faculdade de Medicina/Hospital Universitário Clementino Fraga Filho/Universidade Federal do Rio de Janeiro, 21941-913 Rio de Janeiro, Brazil
Angelo Alves de Mattos, Cristiane Valle Tovo, Serviço de Gastroenterologia e Hepatologia, Irmandade da Santa Casa de Misericórdia/ISCMPA, Porto Alegre, 90020-090 Rio Grande do Sul, Brazil
Lysandro Alsina Nader, Serviço de Endoscopia, Universidade Federal de Pelotas/UFPel, Pelotas, 96010-610 Rio Grande do Sul, Brazil
Juliene Antonio Ramos, Edson Rondinelli, Instituto de Biofísica Carlos Chagas Filho/UFRJ, 21941-902 Rio de Janeiro, Brazil
Arnaldo de Jesus Dominici, Departamento de Gastroenterologia, Hospital Universitário da Universidade Federal do Maranhão/UFMA, São Luis, 65020-560 Maranhão, Brazil
Carlos Eduardo Brandão-Mello, Serviço de Gastroenterologia, Hospital Universitário Gaffrée Guinle/HUGG/UNIRIO, 20270-004 Rio de Janeiro, Brazil
Author contributions: Garcia RFL, Moreira S, Ferreira LE, Pinho MSL and França PHC contributed equally to the study conception and performance, interpretation of data, and writing of the manuscript; Garcia CE performed the statistical analysis and critically reviewed the manuscript for intellectual content; Ramos ALA, de Mattos AA, Tovo CV, Nader LA, Ramos JA, Rondinelli E, Dominici AJ, Brandão-Mello CE and Villela-Nogueira CA contributed equally to the acquisition and analysis of patients’ data.
Supported by Grants from the Research Fund from University of Region of Joinville, FAP-UNIVILLE
Correspondence to: Raquel Francine Liermann Garcia, MD, Departamento de Medicina, Universidade da Região de Joinville/Univille, Rua Paulo Malschitzki, 10, Campus Universitário-Zona Industrial, Joinville, 89219-719 Santa Catarina, Brazil. drargarcia@terra.com.br
Telephone: +55-47-99811610 Fax: +55-47-30291877
Received: January 21, 2013
Revised: August 19, 2013
Accepted: September 4, 2013
Published online: November 14, 2013
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.

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

Core tip: This study investigated the differential distribution of interleukin 28B genetic variants between patients with chronic hepatitis C genotype 1 infection and non-infected healthy controls, and evaluated the association of these polymorphisms with patient response to standard antiviral therapeutic regimens. Genotype and allele frequencies of rs12979860 and rs8099917 were significantly different between the patients and controls, and the patterns suggested a potential protective role against hepatitis C virus infection. Finally, the rs12979860 CC genotype showed correlation to achievement of sustained virological response following pegylated-interferon/ribavirin-based therapy.