ABSTRACT
To assess the role of IL28B rs 12979860 polymorphism in predicting response to treatment in genotype 4 (G4) Egyptian patients, and to evaluate the role of alpha fetoprotein (AFP) in increasing the predictive strength of IL28B rs 12979860 polymorphism to predict response to treatment. One hundred thirty 7 HCV patients were genotyped for IL28B rs 12979860 by polymerase chain reaction--restriction fragment length polymorphism technique. The presence of the C allele of IL28B rs 12979860 was associated with response to treatment, while the T allele was associated with failure of response to treatment. AFP is associated with IL28B rs 12979860 SNP genotypes at cut off 2.68 and 4.5 ng/mL individually. Response rate was 1.3 and 1.6, 3 times higher in CC, CT, and TT respectively in patients below AFP 4.5 ng/mL than in patients above it. IL28B rs 12979860 polymorphism is strongly associated with treatment induced response to treatment. AFP (cut off 4.5 mg/mL) increases the predictive power of IL28B in response to treatment.
Subject(s)
Hepatitis C, Chronic/genetics , Interleukins/genetics , Polymorphism, Genetic , alpha-Fetoproteins/metabolism , Adult , Egypt , Female , Genotype , Hepatitis C, Chronic/therapy , Humans , Interferons , Male , Predictive Value of Tests , Treatment OutcomeABSTRACT
The polymorphism of interleukin 28B (IL28B) rs12979860 is associated with spontaneous and treatment-induced clearance in hepatitis C virus (HCV) genotype 4 (G4). However, there is no information on its interaction with gender, moreover its association with intrahepatic inflammation in North Africans is not studied and its association with fibrosis in North Africans (especially Egyptians) is controversial. This study aims to explore the association between the minor allele of the IL28B rs12979860 polymorphism with gender, fibrosis and necroinflammation in Egyptian G4 HCV patients. IL28B rs12979860 was genotyped in 224 individuals, including 100 healthy controls and 124 consecutive patients with chronic HCV. Results showed (1) IL28B rs12979860 minor alleles associated with susceptibity to chronic HCV mainly in men not women, (2) no association between IL28B rs12979860 with fibrosis and necroinflammation activity, (3) the IL28B rs12979860 TT genotype associated with severe fibrosis in women only and with the necroinflammation activity in men using a recessive model. In conclusion, the IL28B rs12979860 polymorphism is not associated with fibrosis and liver inflammation in Egyptian HCV G4. Nonetheless, the TT genotype of IL28B rs12979860 polymorphism affects the natural history of each gender independently.
Subject(s)
Fibrosis/genetics , Hepacivirus/genetics , Interleukins/genetics , Liver Diseases/genetics , Polymorphism, Genetic/genetics , Sex Characteristics , Adult , Egypt , Female , Fibrosis/blood , Genotype , Humans , Inflammation/genetics , Interferons , Interleukins/blood , Liver Diseases/metabolism , Liver Diseases/virology , MaleABSTRACT
Hepatitis C virus (HCV) infection is a major health problem worldwide. Egypt is the country with the highest HCV infection epidemic in the world. Interleukin (IL)-12 is a cytokine that has been shown to have a potent role as an antiviral cytokine. IL-12 is a heterodimer of the polypeptides p35 and p40. IL-12 B, the gene encoding IL-12 p40, is polymorphic, and a functional single-nucleotide polymorphism (SNP) of the 3'-untranslated region at position rs3212227 was associated with apparent resistance to HCV. The genotype distribution of this polymorphism differs by race. This study is sought to identify the genotype distribution of the IL-12 SNP rs3212227 polymorphism in Egyptians and to assess its role in susceptibility to chronic HCV infection alone or in a sex-dependent way. The study included 238 subjects: 100 healthy controls and 138 patients with HCV infection. The IL-12 SNP rs3212227 was genotyped by the polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP). Results showed a genotype frequency of 46%, 39%, and 15% for AA, AC, and CC IL-12 genotypes, respectively. No significant result (P=0.5) was shown in the differential distribution of the IL-12 SNP genotypes between controls and patients with HCV infection. Nonetheless, this difference in the IL-12 genotype distribution was significant (0.005) when it was stratified according to sex; moreover, the C allele distribution in men and women differed with a statistically high significance (P=0.0001) in controls versus HCV patients. In conclusion, the IL-12 SNP rs3212227 polymorphism confers a susceptibility to HCV infection in a sex-dependent way in Egyptians.