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IL-28 gene single nucleotide polymorphisms (SNPs) genotyping in individuals infected with Hepatitis C virus

Grant number: 10/10549-1
Support Opportunities:Regular Research Grants
Duration: September 01, 2010 - August 31, 2012
Field of knowledge:Biological Sciences - Microbiology - Applied Microbiology
Principal Investigator:João Renato Rebello Pinho
Grantee:João Renato Rebello Pinho
Host Institution: Instituto de Medicina Tropical de São Paulo (IMT). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated researchers: Ana Catharina de Seixas Santos Nastri ; Esper Georges Kallás


Hepatitis C virus (HCV) infection is the leading cause of liver diseases worldwide, with a prevalence rate estimated at 3%. Approximately 30% of individuals infected with HCV spontaneously eliminate it, but most of them evolve to chronic infection that may progress to cirrhosis and liver cancer. Five recent Genome-Wide Association Studies (GWAS) pointed to genetic variations in IL28B gene as predictors for response to treatment with pegylated interferon and ribavirin, as well as a strong association between a polymorphism in the IL28B gene and spontaneous viral clearance. The IL28B gene is located at chromosome 19q13 and encodes a protein known as interferon l (IFN type III). This IFN is structurally related to the superfamily of cytokines such as IL-10 but shares functional characteristics with the type I interferons (IFN-a and IFN-b), which are stimulated by viral infections.The aim of this study is to investigate the frequency of single nucleotide polymorphisms (SNPs) rs12979860 and rs8099917 (located on chromosome 19q13) in individuals infected with HCV genotype 1 with different clinical courses and in a control group of individuals not infected with HCV.No data on the frequency of these different SNPs are available in our country and this work will be the first to deal with their frequency in Brazilian patients, as well as in a control group.Patients with a history of previous or current infection with HCV will be admitted and referred to outpatient clinics at Hepatology Unit, Department of Gastroenterology, Hospital das Clínicas, University of São Paulo Medical School and the Hepatitis Clinics of the Center for Reference and Training for STD / AIDS, divided the following groups:A) 50 patients with spontaneous resolution of HCV infection - defined as the absence of viral RNA detectable by PCR simultaneously with detection of anti-HCV in at least two different times according to the routine of the laboratory services involved. Patients with positive serology for HIV and / or HBsAg will be excluded. Anti-HCV positive results obtained by ELISA will be confirmed by immunoblot (RIBA). Those showing an indeterminate immunoblot result will be tested by ELISpot to confirm or rule out the presence of prior infection with HCV. In this group, a serological test will also be undertaken to determine whether they have been previously infected with genotype 1.B) 50 patients with chronic HCV infection and sustained virological response (SVR) to treatment with pegylated interferon and ribavirin - patients with chronic infection are characterized by positive serology for HCV and the detection of viral RNA by PCR. SVR is defined as the absence of detectable viral RNA by PCR six months after completion of treatment. Patients with positive serology for HIV and / or HBsAg shall be excluded.C) 50 patients non-responders to treatment, i.e., with detectable viral RNA after treatment with pegylated interferon and ribavirin. Patients with positive serology for HIV and / or HBsAg shall be excluded, as well as those with liver cirrhosis.D) Control group of 100 individuals from the general population without prior infection with HCV.Two single nucleotide polymorphisms (SNPs) that are located in the region of the IL28B gene (rs12979860 and rs8099917) will be determined by using real-time PCRStatistical analysis will be performed using the statistical package SPSS (v. 15, SPSS Inc., Chicago, IL). (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
GONZALEZ-ALDACO, KARINA; REBELLO PINHO, JOAO R.; ROMAN, SONIA; GLEYZER, KETTI; FIERRO, NORA A.; OYAKAWA, LETICIA; RAMOS-LOPEZ, OMAR; SANTANA, RUBIA A. FERRAZ; SITNIK, ROBERTA; PANDURO, ARTURO. Association with Spontaneous Hepatitis C Viral Clearance and Genetic Differentiation of IL28B/IFNL4 Haplotypes in Populations from Mexico. PLoS One, v. 11, n. 1, . (10/10549-1)
GONZALEZ-ALDACO, KARINA; PANDURO, ARTURO; PINHO, JOAO R. REBELLO; MARTINEZ-LOPEZ, ERIKA; GLEYZER, KETTI; FIERRO, NORA A.; ROMAN, SONIA. High Prevalence of ITPA Alleles Associated with Ribavirin-Induced Hemolytic Anemia Among Mexican Population. ANNALS OF HEPATOLOGY, v. 16, n. 2, p. 221-229, . (10/10549-1)
ANA LUIZA DIAS ANGELO; LOURIANNE NASCIMENTO CAVALCANTE; KIYOKO ABE-SANDES; TAISA BONFIM MACHADO; DENISE CARNEIRO LEMAIRE; FERNANDA MALTA; JOAO RENATO PINHO; LUIZ GUILHERME COSTA LYRA; ANDRE CASTRO LYRA. Myxovirus resistance, osteopontin and suppressor of cytokine signaling 3 polymorphisms predict hepatitis C virus therapy response in an admixed patient population: comparison with IL28B. Clinics, v. 68, n. 10, p. 1325-1332, . (10/10549-1)

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