Investigation of the Association Between Chronic Hepatitis B and C Infections and Tnf-Α( Gene Polymorphism

Abstract

Cytokines and genetic factors play important roles in the pathogenesis of chronic hepatitis B (CHB) and chronic hepatitis C (CHC) infections. Variations in cytokine genes may effect the gene expression and may lead to changes in the clinical manifestations of diseases. One of the single nucleotide polymorphisms in the promoter region of tumor necrosis factor-alpha (TNF-alpha) gene is the polymorphism at -308. position which was investigated in many studies by means of its relationship between CHB and CHC infections, however their results are incompatible. Furthermore, there is no sufficient data on this subject in our country. This study was aimed to determine the relationship between TNF-a(-308) gene polymorphism with CHB and CHC infections. A total of 271 patients with chronic hepatitis and 181 healthy subjects were included in the study. Of them 167 were CHB cases (67 female, 100 male; age range 18-74 years, mean age: 40.23 +/- 13.09) and 95 controls for CHB group (46 female, 49 male; mean age: 36.41 +/- 15.0 years), while 104 were CHC cases (63 female, 41 male; age range: 25-79 years, mean age: 52.8 +/- 12.6) and 86 controls for CHC group (41 female, 45 male; mean age: 36.4 +/- 14.9 years). After the isolation of genomic DNA from blood samples of the patient and control groups, TNF-alpha(-308)G/A (rs 1800629) polymorphism was investigated by using the real-time polymerase chain reaction from the obtained DNAs. Among CHB group, TNF-alpha(-308) GG, GA, AA genotypes were detected in 126 (75.4%), 38 (22.8%) and 3 (1.8%) of the patients, respectively, while these numbers were 84 (88.4%), 11 (11.6%) and 0 (0%) in control group, respectively. Among CHC group, TNF-a(-308) GG, GA, AA genotypes were detected in 37 (35.6%), 28 (26.9%) and 39 (37.5%) of the patients, respectively, while these numbers were 38 (44.2%), 8 (9.3%) and 40 (46.5%) in control group, respectively. The frequency of GA genotype was significantly higher in both patient groups compared to the control groups (p=0.024 for CHB and p= 0.006 for CHC). When the distribution of allele frequencies of TNF-alpha(-308)G/A polymorphism was evaluated in the patients and control groups, it was noted that G allele was found to be high in CHB patients comparing with controls (94.2% vs 86.8%), however A allele was identified to be lower than controls (5.8% vs 13.2%) (p= 0.008). In contrast, there was no significant difference in terms of allele frequency compared with CHC patients and the control group (p= 0.969). In conclusion, our data in accordance with the results of many studies in literature, determined that TNF-alpha(-308) polymorphisms can influence the chronicity of hepatitis B and C infections. Further studies on this subject would contribute to the elucidation of the molecular mechanisms of chronic hepatitis B and C diseases.