Investigation of the Relationship Between TNF-α, IL-12A, IL-12B and IFN-γ Gene Polymorphisms and Chronic Hepatitis C

Abstract

Hepatitis C virus (HCV) infection is still an important public health problem worldwide. Cytokines play an important role in the prognosis of HCV infections. Polymorphisms in the cytokine genes can affect the gene expression and change the clinical course of the disease. The aim of this study was to determine the relationship between chronic hepatitis C and TNF-α rs1799964 (-1031 T/C), IL-12A rs568408 (3'UTR G/A), IL-12B rs3212227 (3'UTR A/C) and IFN-γ rs2430561 (+874 A/T) gene polymorphisms. A hundred patients with chronic hepatitis C and 100 healthy people as control group were included in the study. Approximately 2 ml peripheral blood was taken from the patient and control groups into tubes with EDTA and genomic DNA was obtained using the DNA isolation kit. Single nucleotide polymorphisms in TNF-α (rs1799964), IL-12A (rs568408), IL-12B (rs3212227) and IFN-γ (rs2430561) genes were investigated by using the real-time polymerase chain reaction (Rt-PCR) method. The data obtained were analyzed in SPSS package program. There was no statistically significant relationship between chronic hepatitis C and TNF-α and IFN-γ polymorphisms in terms of genotype and allele distributions (p> 0.05). However, it was found that the relationship between IL-12A (G/A) and IL-12B (A/C) polymorphisms was significant (p< 0.05). The frequencies of IL-12A GA (OR= 4.828, 95% CI= 1.452-16.046, p= 0.010) and AA genotypes (OR= 4.436, 95% CI= 1.398-14.077, p= 0.011) and A alele (OR= 1.602, 95% CI= 1.020-2.518, p= 0.040) were found to be higher in the patient group. When the relationship between chronic hepatitis C and IL-12B gene polymorphism was examined, it was determined that the frequencies of AC (OR= 2.060, 95% CI= 0.836-5.076, p= 0.116) and CC (OR= 3.020, 95% CI= 1.242-7.345, p= 0.015) genotypes and C allele (OR= 1.750, 95% CI= 1.152-2.659, p= 0.008) were high in the patient group. In addition, TNF-α TC/CC, IL-12A GA/AA, IL-12B AC/CC and IFN-γ TT genotypes were found to be 7.5 times higher in the patient group than the control group (OR= 7.500, 95% CI= 1.532-36.714, p= 0.013). Our results showed that IL-12A (3'UTR G/A) and IL-12B (3'UTR A/C) gene polymorphisms and TNF-α TC/CC, IL-12A GA/AA, IL-12B AC/CC and IFN-γ TT interactions may be effective in the risk of the chronicity of hepatitis C. However, further studies are needed to determine the role of polymorphisms in these cytokine genes in HCV infections.