Abstract

BackgroundGenetic variation in the IL28B gene has been strongly associated with treatment outcomes, spontaneous clearance and progression of the hepatitis C virus infection (HCV). The aim of the present study was to investigate the role of polymorphisms at this locus with progression and outcome of HCV infection in a Moroccan population.MethodsWe analyzed a cohort of 438 individuals among them 232 patients with persistent HCV infection, of whom 115 patients had mild chronic hepatitis and 117 had advanced liver disease (cirrhosis and hepatocellular carcinoma), 68 individuals who had naturally cleared HCV and 138 healthy subjects. The IL28B SNPs rs12979860 and rs8099917 were genotyped using a TaqMan 5′ allelic discrimination assay.ResultsThe protective rs12979860-C and rs8099917-T alleles were more common in subjects with spontaneous clearance (77.9% vs 55.2%; p = 0.00001 and 95.6% vs 83.2%; p = 0.0025, respectively). Individuals with clearance were 4.69 (95% CI, 1.99–11.07) times more likely to have the C/C genotype for rs12979860 polymorphism (p = 0.0017) and 3.55 (95% CI, 0.19–66.89) times more likely to have the T/T genotype at rs8099917. Patients with advanced liver disease carried the rs12979860-T/T genotype more frequently than patients with mild chronic hepatitis C (OR = 1.89; 95% CI, 0.99–3.61; p = 0.0532) and this risk was even more pronounced when we compared them with healthy controls (OR = 4.27; 95% CI, 2.08–8.76; p = 0.0005). The rs8099917-G allele was also associated with advanced liver disease (OR = 2.34; 95% CI, 1.40–3.93; p = 0.0100).ConclusionsIn the Moroccan population, polymorphisms near the IL28B gene play a role both in spontaneous clearance and progression of HCV infection.

Highlights

  • Infection with hepatitis C virus (HCV) is a worldwide health problem, with more than 170 million individuals infected

  • Four independent genome-wide association studies (GWAS) have recently identified several single nucleotide polymorphisms (SNPs) around the interleukin-28B (IL28B) gene, located on chromosome 19q13, coding for IFN-l3, that are strongly associated with treatment outcome and spontaneous hepatitis C virus infection (HCV) clearance [8,9,10,11]

  • We found that the rs12979860-T/T/rs8099917-T/G genotype was present in 19.6% of the advanced group versus 6.9% in mild chronic hepatitis C (mCHC) (p = 0.0035), conferring an odds ratio (OR) of 3.70 for advanced liver disease

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Summary

Introduction

Infection with hepatitis C virus (HCV) is a worldwide health problem, with more than 170 million individuals infected. Four independent genome-wide association studies (GWAS) have recently identified several single nucleotide polymorphisms (SNPs) around the interleukin-28B (IL28B) gene, located on chromosome 19q13, coding for IFN-l3, that are strongly associated with treatment outcome and spontaneous HCV clearance [8,9,10,11]. The rs12979860 SNP lies 3 kb upstream of the IL28B gene whereas rs8099917 is located 8.9 kb from the IFNl3-encoding transcript 39 end in the intergenic region between IFNl2 and IFNl3 These polymorphisms exhibit substantial ethnic diversity in their frequency [8,9,11]. Genetic variation in the IL28B gene has been strongly associated with treatment outcomes, spontaneous clearance and progression of the hepatitis C virus infection (HCV). The aim of the present study was to investigate the role of polymorphisms at this locus with progression and outcome of HCV infection in a Moroccan population

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