Association between Interleukin-21 and Interleukin-21 receptor gene polymorphisms with susceptibility to chronic hepatitis B virus infection and HBV spontaneous clearance in Iranian population.

Hepatitis B virus (HBV) infection is a major public health concern due to the infection often leads to chronic infection, liver cirrhosis and also liver cancer. The host immune response to HBV infection and also genetic background play significant role in outcome of infection. Single nucleotide polymorphisms (SNPs) are the most important kind of variation in genetic sequences that caused by point mutations. As cytokines have major roles in viral infections, it seems that cytokine gene polymorphisms are independently associated with response to viral infections. Interleukin 21 (IL-21) plays an influential role in both innate and adaptive immune responses. Its specific receptor, IL-21R, produced and located on the surface of T, B and natural killer (NK) cells and is critical for the proliferation and differentiation of these immune effector cells. Many studies confirmed that the IL-21 involved in response to viral infections. We aimed to investigate the association of G/T IL-21 (rs2055979) and C/T IL-21R (rs3093390) gene polymorphisms with chronic hepatitis B virus infection and HBV spontaneous clearance in Iranian population. METHODS: In this study, blood samples were gathered from 320 patients with chronic HBV and 310 healthy controls and also 120 HBV spontaneous clearance individuals. Following genomic DNA extraction, genotypes of the selected SNPs determined by PCR and restriction fragment length polymorphism (RFLP) method. The results were analyzed by SPSS software using Chi-square, Logistic Regression, ANOVA and Independent Samples t-Test. RESULTS: According to our results, in IL-21R (rs3093390 C/T) gene polymorphism, allele frequency of T is statistically different in the HBV spontaneous clearance group compared to chronic HBV cases. But there is no significant difference between G/T IL-21 (rs2055979) and C/T IL-21R (rs3093390) genotypes distribution in three groups. Also we found that higher serum aspartate transaminase (AST) level in HBV spontaneous clearance group is significantly associated with TT genotype of IL-21 (rs2055979) compared to GG genotype (P value = 0.006). DISCUSSION: Our results showed that T allele frequency in IL-21R (rs3093390 C/T) gene polymorphism could consider as a host genetic factor for HBV spontaneous clearance. Probably we can serve it as a potential prognostic genetic marker for spontaneous clearance of HBV infection.

Characterization of the "a" determinant region of the hepatitis B virus genome in Iranian patients at different clinical phases of chronic infection.

AIM: To determine the distribution of important mutations of the "a" determinant region in the HBV genome among patients in different clinical phases of HBV infection. BACKGROUND: Variations in Hepatitis B infection not only change the outcome of the disease but also the symptoms from which the chronic HBV patients are suffering. METHODS: We have meticulously selected a total of 40 chronic HBV patients from four different subclasses of chronic HBV clinical phases including immune tolerant (IT), immune active (IA), inactive carrier (IC) and hepatitis B e antigen (HBeAg)-negative (ENEG); 10 samples per each phase. Mutations of the "a" determinant region were identified using PCR-Direct sequencing method. RESULTS: 17 amino-acid substitutions at 12 positions inside the "a" determinant were identified in all forty samples; 3 mutations in the IT group, 6 mutations in the IA phase, 3 mutations in the IC patients and 5 mutations in the ENEG phase. Different substitutions were observed in all four clinical phases. The IA phase was the most variant group with the highest number of amino-acid substitutions. CONCLUSION: These results did not reveal a strong pattern to distinguish different clinical phases of Chronic HBV infection, but there are some obvious differences regarding the number and position of mutations between these four clinical phases.

Interleukin-21 rs2055979 and Interleukin-21 receptor rs3093390 genetic variants and hepatitis C virus chronic infection.

AIM: The aim of this case-control study was to investigate association of G/T IL-21 (rs2055979) and C/T IL-21R (rs3093390) gene polymorphisms with chronic hepatitis C virus in Iranian Patients. BACKGROUND: Interleukin 21 (IL-21) has a significant function in the regulation of cellular immune responses. Its exclusive receptor, IL-21R, expressed on the surface of T, B and NK cells and is important for the proliferation and differentiation of these immune cells. Hence, it was suggested to be involved in response to viral infections. METHODS: This study follows a case-control study design and blood samples were collected from 290 patients with chronic HCV and 290 controls for both genes. Genomic DNA was extracted and then for each position, SNP was genotyped by the dedicated PCR and restriction fragment length polymorphism (RFLP) method. The results were analyzed by SPSS software using logistic regression and Chi-square tests. RESULTS: Genotype frequencies of GG, GT and TT in IL21 gene (rs3093390) were found to be 27.6%, 48.3%, 24.1% and 25.2%, 55,5%, 19,3% respectively in HCV infected patients and control group. For IL21R gene (rs2055979) genotype frequencies of CC, CT and TT were 63.8%, 31.4%, 4.8% and 61.4%, 29.7%, 9.0% respectively in HCV infected patients and control group. P values for genotype and allele frequencies were p=0.188, p=0.769 for IL21 gene, and p=0.144, p=0.179 for IL21R gene respectively. CONCLUSION: As a result, there is no evidence for an association between IL-21 (rs2055979) and IL-21R (rs3093390) gene polymorphisms with chronic hepatitis C virus in Iranian Patients.

Prevalence of hepatitis D virus in hepatitis B virus infected patients referred to Taleghani hospital, Tehran, Iran.

AIM: The aim of this study was to determine the prevalence of HDV infection between HBV chronic patients referred to gastroenterology ward of Taleghani hospital Tehran, Iran and also investigating the risk factors in acquiring the HDV infection. BACKGROUND: Hepatitis B virus (HBV) and Hepatitis D virus (HDV) are major public health issues. Worldwide there are approximately 350 million individuals chronically infected with the HBV. A significant part of them, including 15 to 20 million coinfected with HDV. Hepatitis Delta virus is transferred mostly through blood and body fluids. PATIENTS AND METHODS: HBV and HDV infections were evaluated by Enzyme-linked immunosorbent assay (ELISA). Liver functional tests were assessed through auto analyzer. Patients were interviewed and data along the test results were entered into SPSS program. We used chi-square, independent t-test and logistic regression for statistical analysis. RESULTS: 278 (54.6%) patients of the study group were male and 231 (45.4%) were female and the mean age of patients was 40.03 ± 14.93. From 509 patients, 39(7.7%) had anti-HDV antibody. In a uni-variable analysis, age (p=0.001), periodontal procedures (p=0.015), endoscopy (p=0.024) and colonoscopy (p=0.012) were significantly related to HDV seropositivity. After adjustment by logistic regression, age remained the only significant factor in acquiring HDV infection. CONCLUSION: We highly recommend the health care workers to strictly follow the disinfection protocols of medical instruments. Since HDV seroprevalence changes over time, regular epidemiological studies are necessary to monitor the epidemiological trend of infection.

Lack of Association Between Transforming Growth Factor Beta 1 -509C/T and +915G/C Polymorphisms and Chronic Hepatitis B in Iranian Patients.

BACKGROUND: Chronic hepatitis B is one of the world's major health concerns [corrected]. The etiological agent of this infection is hepatitis B virus (HBV), which can evade the immune system response. Transforming growth factor beta 1 (TGF-ß1) can act against HBV by suppressing the viral replication. The TGF-ß1 also plays an important role in preventing liver damage in chronically HBV infected patients. OBJECTIVES: In this study, the association of TGF-ß1 +915G/C and -509C/T gene polymorphisms with chronic hepatitis B was evaluated in Iranian patients. MATERIALS AND METHODS: A population-based case-control study was conducted in Taleghani Hospital, Tehran. A number of 220 patients with chronic hepatitis B and the same number of healthy control subjects were designated the case and the control groups. The PCR-Restriction Fragment Length Polymorphism Method (PCR-RFLP) method was used for genotyping both polymorphisms. Ten percent of the control samples were sequenced to confirm the results. RESULTS: No statically significant differences in genotype distribution and allele frequency were observed for both polymorphisms between healthy controls and patients with chronic hepatitis B. CONCLUSIONS: There was no association between TGF-ß1 -509C/T and +915G/C polymorphisms with chronic hepatitis B and it seems that these changes do not play a significant role in increasing the risk of chronic infection in Iranian patients [corrected].