ABSTRACT
Ornithine transcarbamylase (OTC) deficiency is an incredibly rare disease in the subgroup of urea cycle disorders. Although typically seen in the neonate shortly after initiating high protein feeds (human breastmilk or infant formula), patients with partial/heterozygous deficiencies can often be diagnosed later in life with unique sequelae. One such manifestation is sudden, transient vision loss shortly after an initial episode of hyperammonemia in a patient without a known diagnosis of OTC deficiency. Only two such occurrences are documented in academic literature and both share many similar presenting features hinting that a hidden, but the consistent pathophysiologic mechanism of this disease is at play. Scarce research is available to propose a concise explanation; however, recent advancements in the literature point toward the brain's inability to uptake glucose and convert it into glutamate in patients with partial OTC deficiency as a likely explanation.
ABSTRACT
Combination regimens of direct-acting antiviral agents (DAAs) for chronic genotype 1 hepatitis C virus (HCV) infection given for 8 or 12 weeks have high cure rates. Shortened treatment durations that maintain high cure rates may lessen treatment barriers related to affordability and drug adherence. We enrolled 12 treatment-naïve adults with chronic genotype 1 HCV infection without cirrhosis in a single-center, open-label trial to receive 2 weeks of the highly potent and selective non-nucleoside inhibitor (NNI) CDI-31244 concurrent with 6 weeks of sofosbuvir/velpatasvir. The main efficacy endpoints were sustained virologic response at 12 (SVR12) and 24 (SVR24) weeks after treatment completion. In all patients, plasma HCV RNA levels rapidly decreased during the first 2 days of treatment and were below the lower limit of quantification by the end of the 6-week treatment period. Eight of 12 (67%) patients achieved both SVR12 and SVR24. Four patients had virological relapse at Week 10, 4 weeks after end of treatment. The most common adverse event was headache, occurring in five (42%) patients. Pharmacokinetic analysis showed no relevant drug interactions between CDI-31244, sofosbuvir, and velpatasvir. In this pilot study of short-duration combination therapy involving a novel NNI with a fixed-combination DAA, 8 of 12 treatment-naïve patients with chronic genotype 1 HCV infection without cirrhosis achieved virologic cure. Future trials might evaluate whether extending the NNI duration beyond 2 weeks with combination DAAs results in higher cure rates comparable with currently approved longer duration therapy.
Subject(s)
Antiviral Agents/therapeutic use , Carbamates/therapeutic use , Hepacivirus/drug effects , Hepatitis C, Chronic/drug therapy , Heterocyclic Compounds, 4 or More Rings/therapeutic use , Sofosbuvir/therapeutic use , Adult , Antiviral Agents/adverse effects , Carbamates/adverse effects , Drug Therapy, Combination , Female , Genotype , Hepacivirus/genetics , Heterocyclic Compounds, 4 or More Rings/adverse effects , Humans , Male , Middle Aged , Pilot Projects , RNA, Viral/blood , Sofosbuvir/adverse effects , Sustained Virologic Response , Time FactorsABSTRACT
Chronic HCV (CHC) infection is the only chronic viral infection for which curative treatments have been discovered. These direct acting antiviral (DAA) agents target specific steps in the viral replication cycle with remarkable efficacy and result in sustained virologic response (SVR) or cure in high (>95%) proportions of patients. These treatments became available 6-7 years ago and it is estimated that their real impact on HCV related morbidity, including outcomes such as cirrhosis and hepatocellular carcinoma (HCC), will not be known for the next decade or so. The immune system of a chronically infected patient is severely dysregulated and questions remain regarding the immune system's capacity in limiting liver pathology in a cured individual. Another important consequence of impaired immunity in patients cleared of HCV with DAA will be the inability to generate protective immunity against possible re-infection, necessitating retreatments or developing a prophylactic vaccine. Thus, the impact of viral clearance on restoring immune homeostasis is being investigated by many groups. Among the important questions that need to be answered are how much the immune system normalizes with cure, how long after viral clearance this recalibration occurs, what are the consequences of persisting immune defects for protection from re-infection in vulnerable populations, and does viral clearance reduce liver pathology and the risk of developing hepatocellular carcinoma in individuals cured with these agents. Here, we review the recent literature that describes the defects present in various lymphocyte populations in a CHC patient and their status after viral clearance using DAA treatments.
Subject(s)
Hepacivirus/immunology , Hepatitis C, Chronic/etiology , Hepatitis C, Chronic/metabolism , Host-Pathogen Interactions/immunology , Lymphocytes/immunology , Lymphocytes/metabolism , Adaptive Immunity , Animals , Antiviral Agents/therapeutic use , Disease Management , Disease Susceptibility , Hepatitis C, Chronic/drug therapy , Humans , Immunity, Innate , Liver/innervation , Liver/metabolism , Liver/pathology , Liver/virology , Lymphocyte Subsets/immunology , Lymphocyte Subsets/metabolism , Viral LoadABSTRACT
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
ABSTRACT
Chronic hepatitis B (CHB) infection functional cure is defined as sustained loss of HBsAg and several therapeutic strategies are in clinical development designed to pharmacologically reduce serum HBsAg, break immune tolerance, and increase functional cure rates. However, little is known about pre-treatment HBsAg levels as an indicator of HBV immune potential. Here, we compared the phenotypes and HBV-specific response of lymphocytes in CHB patients stratified by serum HBsAg levels <500 (HBslo) or >50,000 IU/ml (HBshi) using immunological assays (flow cytometry, ICS, ELISPOT). HBshi patients had significantly higher expression of inhibitory PD-1 on CD4+ T cells, particularly among TEMRA subset, and higher FcRL5 expression on B cells. Upon HBcAg(core) or HBsAg(env)-stimulation, 85% and 60% of HBslo patients had IFNγ+TNFα+ and IFNγ+ IL2+ CD4+ T cell responses respectively, in comparison to 33% and 13% of HBshi patients. Checkpoint blockade with αPD-1 improved HBV-specific CD4+ T cell function only in HBslo patients. HBsAg-specific antibody-secreting cells (ASCs) response was not different between these groups, yet αPD-1 treatment resulted in significantly higher fold change in ASCs among patients with HBsAg <100 IU/ml compared to patients with HBsAg >5,000 IU/ml. Thus, serum HBsAg correlates with inhibitory receptor expression, HBV-specific CD4+ T cell responses, and augmentation by checkpoint blockade.
Subject(s)
B-Lymphocytes/immunology , Hepatitis B Surface Antigens/blood , Hepatitis B virus/immunology , Hepatitis B, Chronic/immunology , T-Lymphocytes/immunology , Biomarkers/blood , Flow Cytometry , Hepatitis B, Chronic/blood , Humans , Programmed Cell Death 1 Receptor/metabolismABSTRACT
Direct acting antiviral (DAA) regimens of 12 weeks result in HCV clearance in vast majority of patients across genotypes. We previously demonstrated an ultra-short regimen of 4 weeks DAA cleared HCV in a subset of patients. Here, we hypothesized that individual level of antiviral immunity differentially influenced viral clearance and investigated biomarkers of a successful response. Cohorts of HCV patients treated for 4 weeks with DAA therapy who either achieved sustained virologic response (SVR) or relapsed were compared at baseline and at end of therapy (EOT) for immune cell phenotypes and HCV specific immunity. Higher levels of PD-1+ CD8+ and CD4+ T lymphocytes co-expressing inhibitory receptors (IR) were present at baseline and at EOT in HCV patients who eventually achieved SVR compared with those who relpased. HCV specific CD8+ T cells were predominantly contained within these IR expressing PD-1+ subsets. Patients in the SVR group had significantly higher CD8+ T cell degranulation in response to HCV peptides at baseline and higher levels of cytokine producing T cells at EOT time-point, relative to those who relapsed. In ex vivo cultures, PD-1+CD160+ CD8+ T cells had higher HCV specific degranulation and PD-1+2B4+ CD8+ T cells had higher cytokine expression (IFNγ+TNFα+ or IFNγ+CD107a+) compared with single or no IR expressing subsets, indicating higher virus specific functional capacity of these subsets. Receiver operating characteristics curve (ROC) for baseline circulating frequencies of PD-1+CD160+, PD-1+Tim-3+ CD8+ T cells and PD-1+CD160+, PD-1+Blimp-1+, PD-1-CTLA4+ CD4+ T cells respectively, had associated C-statistics of 0.8214 and 0.9451 for discriminatin of patients who successfully cleared HCV with 4 weeks treatment. Thus, PD-1+ virus-specific CD8+ T cell subsets with cytotoxic capacity are present in a subset of chronic HCV infected individuals that associate with ability to achieve SVR, indicating role of immunity in DAA mediated viral clearance with short duration therapy.
Subject(s)
Antiviral Agents/therapeutic use , Hepacivirus/drug effects , Hepatitis C, Chronic/drug therapy , Programmed Cell Death 1 Receptor/metabolism , Receptors, Immunologic/metabolism , T-Lymphocytes/drug effects , Adult , Benzimidazoles/therapeutic use , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/virology , Cytokines/metabolism , Drug Therapy, Combination , Female , Fluorenes/therapeutic use , Furans/therapeutic use , Hepacivirus/physiology , Hepatitis C, Chronic/metabolism , Hepatitis C, Chronic/virology , Humans , Male , Middle Aged , Pilot Projects , Quinolines/therapeutic use , Sofosbuvir/therapeutic use , Sustained Virologic Response , T-Lymphocytes/metabolism , T-Lymphocytes/virology , Thiophenes/therapeutic use , Viral Load/drug effectsABSTRACT
Immune dysfunction is a hallmark of chronic HCV infection and viral clearance with direct antivirals recover some of these immune defects. TCRVγ9Vδ2 T-cell dysfunction in treated HCV patients however is not well studied and was the subject of this investigation. Peripheral blood cells from patients who had achieved sustained virologic response (SVR) or those who had relapsed after interferon-free therapy were phenotyped using flow cytometry. Functional potential of Vγ9Vδ2 T cells was tested by measuring proliferation in response to aminobisphosphonate zoledronic acid, and cytotoxicity against HepG2 hepatoma cell line. TCR sequencing was performed to analyse impact of HCV infection on Vδ2 T-cell repertoire. Vγ9Vδ2 cells from patients were activated and therapy resulted in reduction of CD38 expression on these cells in SVR group. Relapsed patients had Vδ2 cells with persistently activated and terminally differentiated cytotoxic phenotype (CD38+ CD45RA+ CD27- CD107a+ ). Irrespective of outcome with therapy, majority of patients had persistently poor Vδ2 T-cell proliferative response to zoledronate along with lower expression of CD56, which identifies anti-tumour cytotoxic subset, relative to healthy controls. There was no association between the number of antigen reactive Vγ2-Jγ1.2 TCR rearrangements at baseline and levels of proliferation indicating nonresponse to zoledronate is not due to depletion of phosphoantigen responding chains. Thus, HCV infection results in circulating Vγ9Vδ2 T cells with a phenotype equipped for immediate effector function but poor cytokine response and expansion in response to antigen, a functional defect that may have implications for susceptibility for carcinogenesis despite HCV cure.
Subject(s)
Antiviral Agents/therapeutic use , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/immunology , Sustained Virologic Response , T-Lymphocytes/pathology , Adult , Aged , Cell Proliferation/drug effects , Clinical Trials as Topic , Cohort Studies , Cytokines/immunology , Cytotoxicity Tests, Immunologic , Female , Hep G2 Cells , Humans , Lymphocyte Activation , Male , Middle Aged , Phenotype , Receptors, Antigen, T-Cell, gamma-delta , T-Lymphocytes/immunology , Zoledronic Acid/pharmacologyABSTRACT
Patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) have higher levels of immune activation, impaired antigen-specific responses, and accelerated fibrogenesis compared to patients monoinfected with HCV. Whether different direct-acting antiviral (DAA) combinations have differential effects on immunophenotypes and functions following successful HCV therapy remain unknown. Therefore, we aimed to assess the peripheral T-cell immunophenotypes and functions in patients coinfected with HIV/HCV who were successfully treated with combination DAA treatment regimens. We analyzed peripheral blood mononuclear cells (PBMCs) at baseline and at the time of sustained viral response (SVR) from subjects treated with three different combination DAA regimens: daclatasvir (DCV) and asunaprevir (ASV) for 24 weeks (CONQUER 2-DAA), DCV/ASV/beclabuvir (BCV) for 12 weeks (CONQUER 3-DAA), and sofosbuvir (SOF) and ledipasvir (LDV) for 12 weeks (ERADICATE study). We used flow cytometry to assess T-cell phenotypes (activation and exhaustion) and HCV-specific T-cell functions (cytokine secretion and cytotoxicity). Statistical analyses were conducted using the Wilcoxon matched-pairs signed-rank test with P < 0.05 considered significant. Overall, there was an improvement in T-cell exhaustion markers, a decrease in T-cell activation, an increase in the effector memory population, and improved T-cell function after achieving SVR, with the largest effects noted with CONQUER 3-DAA treatment. Conclusion: Treatment with DCV/ASV/BCV in patients coinfected with HIV/HCV resulted in greater restoration of the T-cell impairments and perturbations associated with HIV/HCV coinfection to an extent that was greater than that observed in either two-drug regimens. We showed that different DAA-based therapies have different immunologic outcomes after successful HCV treatment in patients coinfected with HIV/HCV. This information will be beneficial for providers when selecting the regimens for patients coinfected with HIV/HCV.
ABSTRACT
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.
ABSTRACT
Gastric cancer (GC) is the second cause of cancer-related death worldwide. Interleukin (IL)-16 has a vital role in the development and homeostasis of the immune system. In the present study, we evaluated an exon variant rs4072111 C/T polymorphism and 3' UTR variant rs1131445 C/T within the miRNA binding with gastric cancer susceptibility in Iranian population. Genomic DNA was isolated from peripheral blood samples according to phenol chloroform extraction. The genotypes of IL-16 polymorphisms rs1131445 T/C and rs4072111 T/C were determined by polymerase chain reaction-restriction fragment length polymorphism method. In this case control study, a total of 256 patients with gastric cancer (238 cases (92.9 %) non-cardia and 18 cases (7.1 %) cardia) and 300 healthy control subjects were evaluated. In the present study, we found a significant association between rs4072111 of IL-16 gene and risk of GC in Iranian population. Individuals with CT genotype showed a significant association with 1.79-fold increased risk of GC (P = 0.008; adjusted OR 1.792; 95 % CI 1.164-2.759). The significant association was also detected for T allele of rs4072111 and increased risk of GC (P < 0.001; adjusted OR 1.981; 95 % CI 1.354-2.900). We also observed statistically a significant relationship between rs1131445 of IL-16 CT genotype and GC risk. Carriers of IL-16 CT genotype compared with TT genotype had 1.44 times higher increased likelihood of GC (P = 0.048; adjusted OR 1.445; 95 % CI 1.003-2.084). After stratification according to gender, we observed that in rs1131445, CT and CC male carriers had a higher risk of GC than females (P = 0.08; adjusted OR 1.608; 95 % CI 0.945-2.737 and P = 0.08; adjusted OR 2.186; 95 % CI 0.897-5.325, respectively). We also observed that for male carriers with C allele in rs1131445, there was a 1.53-fold higher risk of GC risk than female subjects (P = 0.029; adjusted OR 1.53; 95 % CI 1.04.4-2.248). We found that the rs1131445 T/C and rs4072111 T/C variants of IL-16 were significantly associated with increased risk of GC in Iranian population.
Subject(s)
Biomarkers, Tumor/genetics , Genetic Predisposition to Disease/genetics , Interleukin-16/genetics , Polymorphism, Restriction Fragment Length , Polymorphism, Single Nucleotide , Stomach Neoplasms/genetics , Adult , Aged , Area Under Curve , Case-Control Studies , Female , Genotype , Humans , Iran , Male , Middle Aged , Odds Ratio , Polymerase Chain Reaction , ROC Curve , Risk FactorsABSTRACT
Hepatitis C virus (HCV) has infected approximately 170 million people worldwide. While the seroprevalence of anti-HCV antibody among Iranian blood donors is 0.13%, HCV infection is prevalent in 59-80% of Iranian injecting drug users. One hundred seventy-eight anti-HCV positive patients were referred to the Gastroenterology Department at the Taleghani Hospital (Tehran, Iran) between June 2007 and June 2012. Out of 178 samples, 142 were positive for HCV-RNA. HCV subtypes were determined using phylogenetic analysis of the NS5B or 5'UTR/core regions. Of 142 viremic patients, 71 (50%) were infected with HCV subtype 1a, 43 (30.3%) with subtype 3a, 20 (14.1%) with subtype 1b, 3 (2.1%) with subtype 4d, 2 (1.4%) with subtype 4a, 1 (0.7%) with subtype 2b, and 1 (0.7%) with subtype 6a. Interestingly, genetic analysis of a sub-genomic fragment from one patient identified a non-subtypeable HCV genotype-3 strain. There was a significant association between HCV subtype and a history of injecting drug use (P = 0.003). Subtype 3a was predominant among patients with such a history. Injecting drug use was associated with younger age (P < 0.001). HCV subtype was also significantly associated with a history of upper gastrointestinal endoscopy (P = 0.02). Subtype 1a was more frequent among patients with such a history. In addition, history of upper gastrointestinal endoscopy was significantly associated with older age (P = 0.002). In conclusion, while HCV subtype 1a is predominant among infected Iranian individuals, subtype 3a is predominant among Iranian injecting drug users.
Subject(s)
Genetic Variation , Hepacivirus/classification , Hepacivirus/genetics , Hepatitis C/epidemiology , Hepatitis C/virology , 5' Untranslated Regions , Adult , Aged , Aged, 80 and over , Female , Genotype , Hepacivirus/isolation & purification , Humans , Iran/epidemiology , Male , Middle Aged , Molecular Epidemiology , Molecular Sequence Data , Phylogeny , Risk Factors , Sequence Analysis, DNA , Sequence Homology , Viral Nonstructural Proteins/genetics , Young AdultABSTRACT
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].
ABSTRACT
Host genetic background is known as an important factor in patients' susceptibility to infectious diseases such as viral hepatitis. The aim of this study was to determine the effect of genetic polymorphisms of interleukin-16 (IL-16) cytokine on susceptibility of hepatitis B virus (HBV) infected patients to develop chronic HBV infection. Genotyping was conducted using PCR followed by enzymatic digestion and RFLP (restriction fragment length polymorphism) analysis. We genotyped three single nucleotide polymorphisms (SNPs) in the Il-16 gene (rs11556218 T>G, rs4778889 T>C, and rs4072111 C>T) to test for relationship between variation at these loci and patients' susceptibility to chronic HBV infection. Allele frequency of Il-16 gene rs4072111 and rs11556218 was significantly different between chronic HBV patients and healthy blood donors. Genotype frequency of rs4778889 polymorphism of Il-16 gene was significantly different when chronic HBV patients and HBV clearance subjects were compared. Our results showed that Il-16 gene polymorphisms are considerable host genetic factors when we chase biomarkers for prognosis of HBV infected patients.
ABSTRACT
AIM: This study investigated the role of CD86 +237 G/C polymorphism in intensifying the risk of CRC development. BACKGROUND: Colorectal cancer (CRC) is a multi-factorial diseases. Genetic background could affect the susceptibility of individuals to CRC development. CD86 is a co-stimulatory factor on antigen-presenting cells that plays key roles in several cancer related mechanisms such as autoimmunity, transplantation and tumor immunity. PATIENTS AND METHODS: A total of 300 individuals, 150 known CRC patients and 150 healthy control individuals, were subjected for the study. CD86 rs17281995 single nucleotide polymorphism (SNP) was genotyped using Allelic Discrimination method. RESULTS: A statistically significant difference was found among CD86 gene polymorphism (rs17281995) and risk of CRC development. The frequency of GG, GC and CC in control subjects was determined as 38%, 57.3% and 4.7% respectively and in CRC subjects were determined as 42%, 85% and 23% respectively. The data shows a significant association between CC genotype (P = 0.007) and C allele (P = 0.017) of the studied polymorphism and risk of CRC. CC genotype and C allele are also more frequent in female patients when the data is stratified according to gender status. CONCLUSION: Our results suggest that CD86 gene alteration could affect the individual's risk for developing CRC among Iranian population and could be used as an important prognostic factor associated with risk of CRC.
ABSTRACT
AIM: We aimed to investigate the prevalence of Human Bocavirus isolates among Iranian patients suffering from acute gastroenteritis. BACKGROUND: Human Bocavirus is a new parvovirus that has been identified in association with gastroenteritis. Limited data are available about HBoV in Iran. PATIENTS AND METHODS: Viral DNA was extracted from all 294 stool samples. HBoV DNA was detected in extracted samples by polymerase chain reaction (PCR) amplification of a 354 bp of noncapsid protein 1 (NP1) gene. In addition, all samples were also subjected to a nested PCR to amplify a 455 bp of nonstructural 1 (NS1) gene. RESULTS: The main clinical symptoms among HBoV positive patients were diarrhea (77.7%), fever (62.9%), vomiting (55.5%), and anorexia (59.2%). NP1 PCR was positive in 8 samples (2.72%), NS1 was positive in 16 patients (5.44%) and 3 samples had positive results in both regions (1.02%). CONCLUSION: Our results suggest that HBoV could be considered as one of the important etiologic agents of acute gastroenteritis cases in Iran.
ABSTRACT
MicroRNAs (miRNAs) are agents of post-transcriptional gene expression, and they can affect many functions of an individual cell or tissue from extracellular matrix production to inflammatory processes and tumor development. We aimed to determine the possible role of miRNA-binding site polymorphisms located in five cancer-related genes: IL-16, CDKN2A (p16), RAF1, PTGER4, and ITGB4 in colorectal cancer (CRC) risk modification in an Iranian population. This study was performed on 643 individuals (249 CRC cases and 394 healthy controls). We selected five cancer-related genes (IL-16, CDKN2A (p16), RAF1, PTGER4, and ITGB4) and investigated the genotypes of the 3' untranslated region miRNA-binding site polymorphisms in these genes in our study population. The restriction fragment length polymorphism results were confirmed by a direct sequencing method. We found a statistically significant difference between the rs1131445 polymorphism of the IL-16 gene and CRC. The frequencies of the genotypes TT, CT, and CC in controls were 51%, 40.4%, and 8.6%, respectively, and in cases were 41.4%, 44.1%, and 14.5%, respectively, which shows a significant association between the CC genotype of the rs1131445 polymorphism and CRC (P = 0.004). The frequency of the C allele in the CRC group was higher than in the controls, and the C allele of the rs1131445 polymorphism was found to be in association with CRC (P = 0.009). These associations remained significant after Bonferroni's correction for multiple testing. We found that the AA genotype of the rs743554 polymorphism in the ITGB4 gene and the T allele of the rs1051208 polymorphism of the RAF1 gene were associated with the risk of CRC in females; however, after Bonferroni's correction we found that they were non-significant. Finally, we can conclude that a significant relationship exists between the miRNA-binding site polymorphism of the IL-16 gene and CRC risk in the Iranian population.
Subject(s)
Colorectal Neoplasms/ethnology , Colorectal Neoplasms/genetics , Interleukin-16/genetics , MicroRNAs/genetics , Polymorphism, Genetic , Adult , Aged , Binding Sites , Case-Control Studies , Cyclin-Dependent Kinase Inhibitor p16/genetics , Female , Genetic Predisposition to Disease , Genotype , Humans , Inflammation , Integrin beta4/genetics , Iran , Male , Middle Aged , Proto-Oncogene Proteins c-raf/genetics , Receptors, Prostaglandin E, EP4 Subtype/geneticsABSTRACT
AIM: This study investigated the prevalence of sapovirus infections in patient with acute gastroenteritis in Tehran, Iran. BACKGROUND: Sapovirus, a member of the family Caliciviridae is one of the major causative agents of viral gastroenteritis affecting both children and adult individuals. There isn't enough data about prevalence and genotypes of sapovirus infection in Tehran, the capital city of Iran. PATIENTS AND METHODS: A total of 42 fecal samples were collected from patients with acute gastroenteritis from May to July 2009. RT nested- PCR was performed for screening. To genotype the sapovirus isolates, some positive samples were subjected to phylogenetic analysis by sequencing of fragments of viral capsid gene region. RESULTS: Sapovirus was detected in 5 of 42 stool specimens from patients with acute gastroenteritis. Sapovirus detected in this study was clustered into only one distinct genogroup I/2. Sapovirus GI/2 was predominant. CONCLUSION: Our results show that among the studied viruses responsible for this disease, sapovirus was a major viral isolate virus.
ABSTRACT
AIM: Since data about prevalence of JC virus in Iranian population is scarce, this study was designed to evaluate the prevalence of JC virus in healthy individuals who had attended Fajr hospital and Farjam clinical laboratory in Tehran, Iran. BACKGROUND: JC virus is the causative agent of progressive multifocal encephalopathy (PML) in individuals with suppressed immune system. There are some evidences that this virus is responsible for some forms of cancers for example colorectal and gastric cancers in humans. PATIENTS AND METHODS: Urine samples from 133 healthy individuals older than 18 years old were collected and after extraction of viral DNA, PCR was performed to determine the presence of virus. Results of the test and demographic data of subjects were entered into SPSS program and were analyzed by it. RESULTS: 71 subjects were male and 62 individuals were female. Mean age of the population was 42.23 ± 13.47. From the total number of 133 subjects, 51 (38.3%) individuals were positive for the presence of JC virus. Gender had statistically significant relationship with JC virus presence (p= 0.042). Age was not significantly related to JC virus presence status (p= 0.3). CONCLUSION: Obtained rate of JC prevalence in this study is similar to the results of studies in India and Philippine. Because of this virus's role in AIDS and the role of this virus in gastrointestinal cancers have been revealed in recent years, the more extended studies on the prevalence of this virus in different populations in Iran is necessary.
ABSTRACT
Noroviruses are one of important agents that cause acute viral gastroenteritis worldwide. These viruses are belonging to Caliciviridae family and are genetically diverse. To date, there is no valuable data about prevalence of norovirus infection and the dominant genogroup/genotype among Iranian population. The objective of this study was to determine the frequency of norovirus infection in Iranian patients with gastroenteritis referred to three hospitals of Tehran and to specify the dominant genogroup/genotype of this virus among our study population. A total of 293 patients with acute gastroenteritis were included in the study. Detection of norovirus was performed using RT-PCR method and confirmed by direct sequencing with specific designed primers for capsid region of norovirus genome. Phylogenetic analysis was performed using the neighbor-joining method. Norovirus strains identified in our study were subsequently categorized according to previously defined genogroup/genotypes. Of these, norovirus GII was dominant genogroup. Sixty-five percent (17 of 26) of positive samples were determined as GII and 35% (9 of 26) were determined as GI, respectively, in 2008-2009. And among 8 sequenced strains of genogroup II the most frequent genotype was GII.3. The results of this study indicated that norovirus must be considered as one of the infectious causes of acute gastroenteritis among Iranian population. We also found that GII.3 is more prevalent in our study population. To the best of our knowledge there is limited data about the role of noroviruses in children and adults' acute gastroenteritis among Iranian patients and this prevalence and genotyping report of norovirus infection could be remarkable for further studies.
Subject(s)
Caliciviridae Infections/epidemiology , Capsid Proteins/genetics , Gastroenteritis/epidemiology , Norovirus/isolation & purification , Adolescent , Adult , Aged , Aged, 80 and over , Caliciviridae Infections/complications , Caliciviridae Infections/virology , Child , Child, Preschool , Cross-Sectional Studies , DNA Primers/genetics , Feces/virology , Female , Gastroenteritis/complications , Gastroenteritis/virology , Genotype , Humans , Infant , Iran/epidemiology , Male , Middle Aged , Norovirus/classification , Norovirus/genetics , Phylogeny , Prevalence , RNA, Viral/genetics , Reverse Transcriptase Polymerase Chain Reaction , Sequence Analysis, DNA , Young AdultABSTRACT
BACKGROUND: chronic hepatitis B virus (HBV) infection is a multifactorial disease that can result in serious clinical complications. Host genetic background especially the genes that encode immunologic factors like INF-γ and its receptor (IFN-γ R) are critical in the pathogenesis of infection. OBJECTIVES: The current study aimed to investigate the association between two single nucleotide polymorphisms (SNPs) at positions -611 and -56 within the promoter region of gamma interferon receptor1 gene (IFN-γ R1) and chronic HBV infection. MATERIALS AND METHODS: Genomic DNA from peripheral blood samples of 200 chronically HBV infected patients and 200 healthy blood donors, as controls, were collected and genomic DNA was extracted by phenol-chloroform method and DNA analysis genotype identification was performed by PCR-RFLP. RESULTS: The results indicated that both SNP's frequency had a significant difference in the patient and control groups. At position -56, TT genotype was associated with patient group and P value was 0.002 and at position -611, GG genotype was further observed in control group and P value was 0.006. CONCLUSIONS: Presence of G allele at position -611 within promoter of IFN-γ R1 gene in the enrolled population for the study was related to lower risk of disease, and presence of T allele at position -56 was also related to susceptibility to chronic HBV infection. Men had higher frequency of chronic HBV infection, which might be the result of high risk behavior.