Investigation of correlation between genetic polymorphism in HAD-1 and HBD-1 genes with progression and severity of Hepatitis C infection in a group of Iraqi patients

Hepatitis C virus (HCV) is a single-stranded RNA virus. Eight viral genotypes and more than 67 HCV subtypes have been identified to date. Acute hepatitis develops in 15% of patients infected with HCV, and chronic infection in 80%. An estimated 71 million people worldwide are chronically infected with HCV. Cirrhosis develops in 20% of chronically infected patients within 25 years, and hepatocellular carcinoma develops in 25% of cirrhotic patients. Acute HCV infection, which is symptomatic, develops in <30% of patients. Approximately 30% of infected individuals spontaneously clear HCV within 6 months. At least 60–80% of individuals develop chronic HCV infection, defined as the presence of anti-HCV antibodies and the persistence of HCV RNA in the blood for at least 6 months. This cross-sectional study included two study groups as 100 male patients with laboratory-confirmed HCV infection and 80 healthy male blood donors as a control group. Participants' anti-HCV Ab, total serum bilirubin, ALT, AST, alkaline phosphatase, erythrocyte sedimentation rate, complete blood count measurements and IL-6, IL-28, IFN-γ, TNFα, Human Beta defensin 1 (HBD-1) and Human Alpha defensin-1 (HAD-1) determinations were completed. Molecular techniques were also applied for the patients and HCV nucleotide sequences were obtained. SAS software was used in the statistical analysis of the data, ANOVA, t-test, Mann-Whitney test and ROC curves were applied. P < 0.05 was considered statistically significant. Chi-square test was also used to determine whether the population was in H-W balance. Correlation coefficient was calculated between the markers in the patients. The results showed that IL-28, IL-6, TNF-α, IFN-γ, HBD-1 and HAD-1 levels were significantly higher in patients than in controls (P<0.01). In complete blood count; white blood cell (WBC), granulocyte, erythrocyte (RBC) and platelet counts were found to be significantly higher in patients, while Hb levels were found to be low. Liver enzymes and bilirubin levels were also high in patients. A positive correlation was found between HBD-1 and HAD-1 (r=0.274, P=0.006), and a negative correlation was found between HBD-1 and TNF-α and IFN-γ (r=-0.340, P=0.001 and r=-0.229, P=0.022, respectively). Molecular analyses showed that there were single nucleotide polymorphisms (SNPs) in the HBD-1 and HAD-1 genes and that these SNPs had a significantly higher frequency in patients. The study revealed that HBD-1 and HAD-1 were significantly expressed in HCV-infected patients, correlated with cytokines, and may play a role in HCV pathogenesis. These findings shed light on the immunopathogenesis of HCV infection.