Novel long noncoding RNAs upregulation may have synergistic effects on the CYP24A1 and PFDN4 biomarker role in human colorectal cancer.

Long noncoding RNAs (lncRNAs) are emerging as the master regulators of tumor initiation, proliferation, and metastasis; however, their diagnostic value as potential biomarkers should be clarified. Vitamin D influences the expression of several genes in various pathways, including the CYP24A1 gene in the vitamin D metabolism pathway. In the present research, we surveyed the expression levels and clinical significance of novel lncRNAs related to CYP24A1 and PFDN4 genes in colorectal cancer (CRC) using real-time polymerase chain reaction. Furthermore, we assessed the expression of these genes after vitamin D treatment in HCT-116 and HT-29 colon cancer cell lines. Our results indicated that the transcription of CYP24A1, PFDN4, and nearby lncRNAs was affected by vitamin D treatment in HCT-116 and HT-29 cell lines. Moreover, CYP24A1, PFDN4, lnc-CYP24A1-3:1, and lnc-TSHZ2-19:1 were upregulated and had the potential to distinguish colorectal cancer tissues from the adjacent tissues by the large area under the receiver operating characteristic curve (0.94, 0.66, 0.70, and 0.60, respectively). lnc-TSHZ2-19:1 expression level significantly correlated with gender (p = .03). In conclusion, CYP24A1, PFDN4, lnc-CYP24A1-3:1, and lnc-TSHZ2-19:1 can be used as potential diagnostic biomarkers in the specific and sensitive assessment of CRC. Besides this, vitamin D treatment may modulate the expression of these genes in a cell-specific manner.

ROC-king onwards: intraepithelial lymphocyte counts, distribution & role in coeliac disease mucosal interpretation.

OBJECTIVES: Counting intraepithelial lymphocytes (IEL) is central to the histological diagnosis of coeliac disease (CD), but no definitive 'normal' IEL range has ever been published. In this multicentre study, receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off between normal and CD (Marsh III lesion) duodenal mucosa, based on IEL counts on >400 mucosal biopsy specimens. DESIGN: The study was designed at the International Meeting on Digestive Pathology, Bucharest 2015. Investigators from 19 centres, eight countries of three continents, recruited 198 patients with Marsh III histology and 203 controls and used one agreed protocol to count IEL/100 enterocytes in well-oriented duodenal biopsies. Demographic and serological data were also collected. RESULTS: The mean ages of CD and control groups were 45.5 (neonate to 82) and 38.3 (2-88) years. Mean IEL count was 54±18/100 enterocytes in CD and 13±8 in normal controls (p=0.0001). ROC analysis indicated an optimal cut-off point of 25 IEL/100 enterocytes, with 99% sensitivity, 92% specificity and 99.5% area under the curve. Other cut-offs between 20 and 40 IEL were less discriminatory. Additionally, there was a sufficiently high number of biopsies to explore IEL counts across the subclassification of the Marsh III lesion. CONCLUSION: Our ROC curve analyses demonstrate that for Marsh III lesions, a cut-off of 25 IEL/100 enterocytes optimises discrimination between normal control and CD biopsies. No differences in IEL counts were found between Marsh III a, b and c lesions. There was an indication of a continuously graded dose-response by IEL to environmental (gluten) antigenic influence.

Lack of Association between NOD2 rs3135500 and IL12B rs1368439 microRNA Binding Site SNPs and Colorectal Cancer Susceptibility in an Iranian Population.

OBJECTIVE: The purpose of this study was to evaluate the potential association between single nucleotide polymorphisms (SNPs) in microRNA (miRNA) binding sites in the NOD2 and IL12B gene 3.-untranslated regions and colorectal cancer (CRC) susceptibility in an Iranian population. METHODS: We genotyped NOD2 rs3135500 [3. untranslated region (UTR) A/G] and IL12B rs1368439 (3.UTR G /T) in a hospital-based study of 92 colorectal cancer cases and 105 healthy controls. All samples were genotyped by TaqMan assay via an ABI 7500 Real Time PCR System (Applied Biosystems) with DNA from FFPE tissue and peripheral blood. RESULTS: our results showed similar distribution of genotype and allelic frequencies of the NOD2 and IL12B polymorphisms between patients and controls. When the more common rs3135500 AA genotype was used as the reference, the rs3135500 AG and rs3135500 GG genotypes were not significantly associated with the risk of CRC (OR = 1.294, 95% CI: 0.524 -3.197; and OR = 2.230, 95% CI: 0.87 - 5.715, respectively), and The IL12B rs1368439 TG and IL12B rs1368439 GG genotypes were not significantly associated with the risk of CRC compared with the IL12B rs1368439 TT genotype (OR = 1.547 95% CI: 0.187- 12.771; and OR = 1.753, 95% CI: 0.217-14.157, respectively). CONCLUSION: NOD2 rs3135500 and IL12B rs1368439 SNPs were not genetic risk factors for colorectal cancer in the studied Iranian population.

Prevalence of inflammatory bowel disease among patients with primary sclerosing cholangitis in Iran.

BACKGROUND AND STUDY AIMS: In Iran, the epidemiology of primary sclerosing cholangitis (PSC) and its association with inflammatory bowel disease (IBD) have not been studied thoroughly. This study investigates the epidemiology and prevalence of IBD among patients with PSC. PATIENTS AND METHODS: A retrospective study of 154 patients with PSC was conducted. The demographic and clinical data were collected, and the variables were analysed in the following two patient groups: patients with both PSC and IBD, and patients with PSC and without IBD. RESULTS: A total of 154 patients with a mean age of 40.3years (range 20-81years) were included, of whom 57 (37%) were female and 97 (63%) male. Ninety-six patients (62.3%) were diagnosed with IBD, 92 (59.7%) with ulcerative colitis, and four (2.6%) with Crohn's disease. In this study, elevated alkaline phosphatase levels were found in 90.8% of patients. The intra-hepatic duct (IHD) and extrahepatic duct (EHD) were involved in 70.5% of patients, isolated intrahepatic bile duct in 24.4%, and isolated extrahepatic duct in 3.8%. Small-duct PSC (normal results of imaging and PSC proved by histology of liver biopsy) was observed only in 1.3% of patients. CONCLUSION: PSC has become increasingly diagnosed in Iran. This is possibly because of better diagnostics and the increasing prevalence of IBD in this country. For diagnosing PSC and identifying the presence of IHD strictures, the results of both magnetic resonance cholangiopancreatography (MRCP) and endoscopic retrograde cholangiopancreatography (ERCP) showed good interobserver agreement, but the ERCP results could be used to evaluate the presence and severity of EHD strictures.

The role of the intensive care unit environment and health-care workers in the transmission of bacteria associated with hospital acquired infections.

The goal of this study was to attempt to determine the rate of contamination of health-care workers' (HCWs) hands and environmental surfaces in intensive care units (ICU) by the main bacteria associated with hospital acquired infections (HAIs) in Tehran, Iran. A total of 605 and 762 swab samples were obtained from six ICU environments and HCWs' hands. Identification of the bacterial isolates was performed according to standard biochemical methods, and their antimicrobial susceptibility was determined based on the guidelines recommended by clinical and laboratory standards institute (CLSI). The homology of the resistance patterns was assessed by the NTSYSsp software. The most frequent bacteria on the HCWs' hands and in the environmental samples were Acinetobacter baumannii (1.4% and 16.5%, respectively), Staphylococcus aureus (5.9% and 8.1%, respectively), S. epidermidis (20.9% and 18.7%, respectively), and Enterococcus spp. (1% and 1.3%, respectively). Patients' oxygen masks, ventilators, and bed linens were the most contaminated sites. Nurses' aides and housekeepers were the most contaminated staff. Imipenem resistant A. baumannii (94% and 54.5%), methicillin-resistant S. aureus (MRSAs, 59.6% and 67.3%), and vancomycin resistant Enterococci (VREs, 0% and 25%) were detected on the hands of ICU staff and the environmental samples, respectively. Different isolates of S. aureus and Enterococcus spp. showed significant homology in these samples. These results showed contamination of the ICU environments and HCWs with important bacterial pathogens that are the main risk factors for HAIs in the studied hospitals.

Device-associated infection rates and bacterial resistance in six academic teaching hospitals of Iran: Findings from the International Nocosomial Infection Control Consortium (INICC).

Device-associated health care-acquired infections (DA-HAIs) pose a threat to patient safety, particularly in the intensive care unit (ICU). However, few data regarding DA-HAI rates and their associated bacterial resistance in ICUs from Iran are available. A DA-HAI surveillance study was conducted in six adult and pediatric ICUs in academic teaching hospitals in Tehran using CDC/NHSN definitions. We collected prospective data regarding device use, DA-HAI rates, and lengths of stay from 2584 patients, 16,796 bed-days from one adult ICU, and bacterial profiles and bacterial resistance from six ICUs. Among the DA-HAIs, there were 5.84 central line-associated bloodstream infections (CLABs) per 1000 central line-days, 7.88 ventilator-associated pneumonias (VAPs) per 1000 mechanical ventilator-days and 8.99 catheter-associated urinary tract infections (CAUTIs) per 1000 urinary catheter-days. The device utilization ratios were 0.44 for central lines, 0.42 for mechanical ventilators and 1.0 for urinary catheters. The device utilization ratios of mechanical ventilators and urinary catheters were higher than those reported in the ICUs of the INICC and the CDC's NHSN reports, but central line use was lower. The DA-HAI rates in this study were higher than the CDC's NHSN report. However, compared with the INICC report, the VAP rate in our study was lower, while the CLAB rate was similar and the CAUTI rate was higher. Nearly 83% of the samples showed a mixed-type infection. The most frequent pathogens were Acinetobacter baumannii, Staphylococcus aureus and Pseudomonas aeruginosa, followed by Klebsiella pneumoniae and Enterococcus spp. In the S. aureus isolates, 100% were resistant to oxacillin. Overall resistances of A. baumannii and K. pneumonia to imipenem were 70.5% and 76.7%, respectively. A multiple drug resistance phenotype was detected in 68.15% of the isolates. The DA-HAI rates in Iran were shown to be higher than the CDC-NHSN rates and similar to the INICC rates. Resistance to oxacillin and imipenem was higher as well. Comparing device use, DA-HAI rates, and bacterial resistance for the primary isolated bacteria indicated a direct association between urinary catheter use and the rates of CAUTI.

Novel effects of Helicobacter pylori CagA on key genes of gastric cancer signal transduction: a comparative transfection study.

Helicobacter pylori (H. pylori) infection is now recognized as a worldwide problem. Helicobacter pylori CagA is the first bacterial oncoprotein to be identified in relation to human cancer. Helicobacter pylori CagA is noted for structural diversity in its C-terminal region (contains EPIYA motifs), with which CagA interacts with numerous host cell proteins. Deregulation of host signaling by translocated bacterial proteins provides a new aspect of microbial-host cell interaction. The aim of this study is to compare the cellular effects of two different CagA EPIYA motifs on identified signaling pathways involve in gastric carcinogenesis. To investigate the effects of CagA protein carboxyl region variations on the transcription of genes involved in gastric epithelial carcinogenesis pathways, the eukaryotic vector carrying the cagA gene (ABC and ABCCC types) was transfected into gastric cancer cell line. The 42 identified key genes of signal transduction involved in gastric cancer were analyzed at the transcription level by real-time PCR. The results of real-time PCR provide us important clue that the ABCCC oncoprotein variant can change the fate of the cell completely different from ABC type. In fact, these result proposed that the ABCCC type can induce the intestinal metaplasia, IL-8, perturbation of Crk adaptor proteins, anti-apoptotic effect and carcinogenic effect more significantly than ABC type. These data support our hypothesis of a complex interaction of host cell and these two different H. pylori effector variants that determines host cellular fate.

Antibiotic susceptibility profile of Helicobacter pylori isolated from the dyspepsia patients in Tehran, Iran.

BACKGROUND/AIM: Helicobacter pylori is an important pathogen for gastroduodenal diseases. Infection with H. pylori can be limited by regimens of multiple antimicrobial agents. However, antibiotic resistance is a leading cause of treatment failure. The aim of this study has been to determine the resistance patterns of H. pylori strains isolated from gastric biopsies of patients with dyspepsia by agar dilution method, in Tehran, Iran. PATIENTS AND METHODS: H. pylori isolates from patients with gastrointestinal diseases were evaluated for susceptibility testing by agar dilution method. Susceptibility testing was performed to commonly used antibiotics including clarithromycin, tetracycline, amoxicillin, metronidazole and ciprofloxacin. RESULTS: Among 92 patients with dyspepsia, H. pylori strains were isolated from 42 patients. Seventeen (40.5%) of the isolates were resistant to metronidazole (MICs ≥ 8 µg/l), whereas one isolate (2.4%) was resistant to amoxicillin (MICs ≤ 0. 5 µg/ml) and ciprofloxacin (MICs ≤ 1µg/ml). The resistance rates to other antibiotics in H. pylori isolates are recorded as follows: clarithromycin 6 (14.3 %), tetracycline 2 (4.8%). In 5 of 42 resistant cases, combined resistance was found. CONCLUSIONS: These data suggest that metronidazole should be used among Iranian patients in first-line therapy with caution, and ciprofloxacin in association with amoxicillin and a proton pump inhibitor is more recommended.

Rotavirus and coeliac autoimmunity among adults with non-specific gastrointestinal symptoms.

OBJECTIVE: To determine celiac disease (CD) serology and rotavirus (RV) by polymerase reaction (PCR) in adults with non-specific gastrointestinal complaints. METHODS: The study comprised 5176 randomly selected individuals living in Tehran, Iran between September 2006 and September 2007. Six hundred and seventy individuals with GI symptoms were identified with a questionnaire and invited for a further study including stool sampling and blood tests. Stool samples were examined for detection of RV by amplification of specific gene (VP6) and by light microscopy and formalin-ether concentration methods for parasite detection. The subjects also tested for CD including anti-transglutaminase (tTG) antibodies and total immunoglobulin A (IgA). The study was carried out in the Research Center of Gastroentrology and Liver Disease, Taleghani Hospital, Tehran, Iran. RESULTS: The VP6 gene was detected in 150 (22.3%) individuals. Anti-tissue transglutaminase (tTG-IgA) was positive in 22 individuals (95% CI 2.3-5.1) and IgG-tTG antibody in 3 individuals who were IgA deficient. Amplification of VP6 gene was positive in 8/25 (32%) with positive CD serology and in 142/645 (22%) with negative CD serology. This difference was not statistically significant (p=0.2). CONCLUSION: This study shows that RV infection is common among Iranian patients with non-specific gastrointestinal symptoms. However, in contrast to studies in children, this study shows that the prevalence of active RV infection was not statistically significantly different between individuals who were tTG antibody positive and those who were tTG antibody negative.

Endoscopic retrograde cholangiopancreatography outcome from a single referral center in Iran.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is the first choice for diagnostic evaluation of the pancreatic and biliary tree and can be accompanied by a high diagnostic sensitivity and a poor therapeutic outcome. In the current study, we described our experiences in the indications, findings, and technical success of ERCP in a sample of the Iranian population admitted to a referral center in Iran. METHODS: In a retrospective review database-based study, 780 patients (393 males and 387 females; mean age 57.5 years) who had undergone diagnostic and therapeutic ERCP with the primary diagnosis of hepatobiliary disorder between 2006 and 2008 at Taleghani Hospital in Tehran were reviewed. The key data were demographic characteristics, clinical information, laboratory parameters, as well as post-ERCP complications. RESULTS: A history of cholecystectomy was found in about one-third (36.3%) of participants and 80 (10.3%) out of 780 patients had a previous history of biliary stone. A minority (1.4%) of the patients suffered from hepatobiliary carcinomas, and 11 patients had cirrhosis. The most common clinical manifestations in the patients undergoing diagnostic ERCP were icterus (47.3%), weight loss (31.2%), and dark urine (26.9%). Selective biliary cannulation was technically successful in 87.0% of the patients; however, cannulation failed in 13.0%. The most frequent final diagnosis of ERCP was common bile duct stone that was detected in 40.1% of the patients. The ERCP results in 11.0% of the patients were normal. Regarding appropriate treatment, successful stenting was performed in 43 patients (15.2%). Among post-ERCP complications, pancreatitis was the most adverse event with an incidence rate of 3.3%. Other complications including local bleeding, cholangitis and gastrointestinal perforation, rarely occurred. Post-ERCP pancreatitis was reported in 1.8% of men and 3.6% of women (P=0.120). Pancreatitis was more common in women below 70 years than in those who were older than 70 years (3.6% versus 0.5%; OR: 8.216, P=0.015). This might be due to the more functionally active pancreas in younger women than in the older ones. However, other complications were similar in the two age groups. CONCLUSIONS: Based on our experience, ERCP indications, final diagnosis and related complications are comparatively consistent with those reported in other countries. The most common post-ERCP complication is pancreatitis that is more often observed in younger patients.

Functional bowel disorders in Iranian population using Rome III criteria.

BACKGROUND/AIM: To study the prevalence and risk factors of functional bowel disorders (FBD) in Iranian community using Rome III criteria. MATERIALS AND METHODS: This study was a cross-sectional household survey conducted from May 2006 to December 2007 in Tehran province, Iran, including 18,180 participants who were selected randomly and interviewed face-to-face by a validated questionnaire based on Rome III criteria. RESULTS: In all, 1.1% met the Rome III criteria for irritable bowel syndrome (IBS), 2.4% for functional constipation (FC), and 10.9% of the participants had any type of FBD. Among participants with functional dyspepsia, 83.8% had FBD; the majority cases were unspecified functional bowel disorder (U-FBD). Of the subjects fulfilling the IBS criteria, IBS with constipation (52%) was the most frequent subtype. In the multivariate analysis, women had a higher risk of any FBDs than men, except for functional diarrhea (FD). The prevalence of FBD, FC and FD increased and IBS decreased with increasing age. Marital status was only associated with a decrease in the risk of FBD and FD, respectively. IBS subtypes compared with FC and FD. There was no significant difference between FC and IBS with constipation (IBS-C), except for self-reported constipation; while, IBS with diarrhea (IBS-D) had more symptoms than FD. CONCLUSION: This study revealed a low rate of FBDs among the urban population of Tehran province. The ROME III criteria itself, and the problems with interpretation of the data collection tool may have contributed in underestimating the prevalence of FBD. In addition the reliability of recall over 6 months in Rome III criteria is questionable for our population.

CTL escape mutations of core protein are more frequent in strains of HBeAg negative patients with low levels of HBV DNA.

BACKGROUND: Recent studies have suggested that Cytotoxic T lymphocytes (CTL) play a key role in eliminating hepatitis B virus (HBV). OBJECTIVES: We aimed to investigate the role of mutations in different immune epitopes of hepatitis B core antigen (HBcAg) among Iranians with hepatitis B e antigen negative chronic hepatitis B (e-CHB), and asymptomatic carriers (ASCs). STUDY DESIGN: Amino acids 1-150 of HBcAg were characterized for HBV strains from 29 e-CHB patients and 48 ASCs from Iran. All patients were infected with HBV genotype D and had previously been investigated for the presence of pre-core and basic core promoter (BCP) mutants. RESULTS: Amino acid mutations of core protein were observed more frequently in HBV strains from ASCs than e-CHB patients (p=0.014). Asn(67) mutation was mutually exclusive to the combination Ile(66) and Ser(69) (P<0.001). Substitutions for Ser(21) and Thr12Ser were associated with lower serum levels of HBV DNA (p<0.001). None of the patients with mutations in HLA-A2 CTL epitope, 18-27, had serum HBV DNA more than 10(5)copies/mL (p<0.001). By multivariate analysis, high level (>10(5)copies/mL) of serum HBV DNA was inversely associated with the presence of mutations in CTL epitopes of HBc (OR: 0.11, p=0.015), while it was directly associated with the presence of promoter double T(1762)A(1764) mutations together with G(1757) (OR: 16.87, p=0.004). CONCLUSION: The inverse correlation between serum levels of HBV DNA and CTL escape mutations of the core protein in HBeAg seroconverted patients, supports the notion that selection of CTL escape mutations consolidates the persistence of HBV infection despite reducing viral fitness.

Distribution of Helicobacter pylori cagA, cagE, oipA and vacA in different major ethnic groups in Tehran, Iran.

BACKGROUND AND AIM: There are geographical variations in Helicobacter pylori virulence genes; cagA, cagE, vacA and oipA. The present study compared the distribution of these genotypes in major ethnic groups residing in Tehran, Iran and their association with clinical outcomes. METHODS: A total of 124 H. pylori-positive patients living in Tehran were enrolled in this study. The ethnic distribution was 74 Persians, 33 Turks and 17 other ethnics including Kurds, Lurs, Afghanis and Arabs. The presence of the cagA, cagE and oipA genes and vacA alleles (signal [s] and middle [m] region) were determined by polymerase chain reaction (PCR) from H. pylori DNA. RESULTS: The cagA-positive status was predominant in all three ethnic groups (e.g. 65% in Persians and 73% in Turks). In contrast, the cagE-positive status was less than half in Persians (47%) and Turks (30%), whereas it was 77% in other ethnicities (P = 0.008). The predominant vacA genotypes were s1 and m1 in all three ethnic groups (e.g. 68% in Persians and 70% in Turks were s1). There was no significant association between cagA and cagE status or vacA genotypes and clinical outcomes. The oipA-positive strains were more common in non-ulcer dyspepsia (NUD) (63%) than in peptic ulcer patients (15%) (P = 0.001) in Persians, but the association was not observed in other ethnic groups. CONCLUSION: There are some differences in the H. pylori genotypes among the ethnic groups in Iran. However, none of these markers seemed to be clinically helpful in predicting the clinical presentation of a H. pylori infection in Iran.

Comparison of colorectal and gastric cancer: survival and prognostic factors.

BACKGROUND/AIMS: Gastric and colorectal cancers are the most common gastrointestinal malignancies in Iran. We aim to compare the survival rates and prognostic factors between these two cancers. METHODS: We studied 1873 patients with either gastric or colorectal cancer who were registered in one referral cancer registry center in Tehran, Iran. All patients were followed from their time of diagnosis until December 2006 (as failure time). Survival curves were calculated according to the Kaplan-Meier Method and compared by the Log-rank test. Multivariate analysis of prognostic factors was carried out using the Cox proportional hazard model. RESULTS: Of 1873 patients, there were 746 with gastric cancer and 1138 with colorectal cancer. According to the Kaplan-Meier method 1, 3, 5, and 7-year survival rates were 71.2, 37.8, 25.3, and 19.5%, respectively, in gastric cancer patients and 91.1, 73.1, 61, and 54.9%, respectively, in patients with colorectal cancer. Also, univariate analysis showed that age at diagnosis, sex, grade of tumor, and distant metastasis were of prognostic significance in both cancers (P < 0.0001). However, in multivariate analysis, only distant metastasis in colorectal cancer and age at diagnosis, grade of tumor, and distant metastasis in colorectal cancer were identified as independent prognostic factors influencing survival. CONCLUSIONS: According to our findings, survival is significantly related to histological differentiation of tumor and distant metastasis in colorectal cancer patients and only to distant metastasis in gastric cancer patients.

Uninvestigated dyspepsia and its related factors in an Iranian community.

OBJECTIVE: To determine the prevalence and determinants of uninvestigated dyspepsia in the Iranian population. METHODS: A cross-sectional study conducted in Tehran province from May 2006 to December 2007, included 18,180 adult persons selected randomly. The study took place at Shahid Beheshti University, MC, Tehran, Iran. A questionnaire was completed in 2 steps. In the first part, personal characteristics and 11 gastrointestinal symptoms were inserted. Those who reported at least one of these 11 symptoms were referred for the second interview, which consisted of questions on different gastrointestinal disorders based on Rome III criteria, including uninvestigated dyspepsia. RESULTS: The prevalence rate of uninvestigated dyspepsia was 8.5% (10.9% in women and 6.4% in men). Among the subjects diagnosed with dyspepsia, bothersome postprandial fullness was the most common symptom (41.5%). Uninvestigated dyspepsia was more common in low educated and widowed participants. Approximately 41.4% of patients had a history of depression, and 66.1% had self report of stress. The prevalence of functional irritable bowel syndrome in patients with uninvestigated dyspepsia was 8.3% and gastroesophageal reflux disease was 64.9%. CONCLUSION: Uninvestigated dyspepsia has a less common prevalence in the general Iranian population than developed countries. Women, older, obese, widowed, and low education subjects are more likely to suffer from dyspepsia.

Association of vitamin D receptor gene polymorphisms in Iranian patients with inflammatory bowel disease.

BACKGROUND AND AIMS: The vitamin D receptor (VDR) gene maps to a region on chromosome 12 shown to be linked to inflammatory bowel disease (IBD). Many studies have recognized the relation of VDR gene polymorphisms with inflammatory and autoimmune disorders. Determining the frequency of these polymorphisms and their possible relation with IBD can improve understandings about the genetic background of these diseases. The objective of this study was to assess the association of VDR gene polymorphisms (Apa I, Taq I, Bsm I, Fok I) with IBD in Iran. METHODS: In this case control designed study 150 patients with ulcerative colitis, 80 patients with Crohn's disease and 150 Age and Sex matched healthy controls from Iranian origin were enrolled. These patients were referred to a tertiary center during a two-year period (2004-2006). Assessment of VDR gene polymorphisms was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The genotype-phenotype association for these polymorphisms was analyzed. RESULTS: Only the frequency of the Fok I polymorphism was significantly higher in ulcerative colitis and Crohn's groups. The frequency of the polymorphic allele f was higher in ulcerative colitis and Crohn's patients comparing with controls (P = 0.011 and P < 0.001, respectively). The f/f genotype was also significantly more frequent (P < 0.001), while the F/F genotype was less presented in Crohn's patients compared to controls (P < 0.001). No genotype-phenotype association was observed with any mutations. CONCLUSIONS: This study suggests a probable association of the Fok I polymorphism in VDR receptor gene and Crohn's susceptibility in Iranian population.

Serum measures of iron status and HFE gene mutations in patients with hepatitis B virus infection.

AIM: We tested associations between HFE mutations and hepatitis B virus (HBV) infection. We also explored measures of total body iron status and their association with chronic HBV infection. METHODS: Serum measures of iron status and HFE mutations (C282Y, H63D, and S65C) were assessed in 344 Iranian patients with chronic HBV infection (214 asymptomatic carriers, 130 patients with chronic progressive liver disease [CPLD]) and 302 controls. RESULTS: Frequencies of HFE mutations did not differ between patients with chronic HBV infection and controls (C282Y: P=0.9, H63D: P= 0.8, S65C: P=0.9). By logistic regression, advanced hepatic fibrosis was associated with HFE H63D mutation (OR=13.1, P=0.006; 95% CI=2.0-84.1). Higher levels of serum ferritin and transferrin saturation were observed in patients with CPLD than in healthy controls (P=0.0001 and 0.01, respectively, adjusted for age and sex). None of the serum iron measures was related to liver fibrosis stage or necroinflammatory grade. CONCLUSION: Serum iron measures are associated with chronic progressive hepatitis B. Carriage of HFE mutations is not associated with the presence of chronic HBV infection or values of serum iron measures in this population, although HFE H63D is associated with more advanced hepatic fibrosis.

T1764G1766 core promoter double mutants are restricted to Hepatitis B virus strains with an A1757 and are common in genotype D.

To investigate the role of pre-core and basal core promoter (BCP) mutants in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (e-CHB) in Iran, Hepatitis B virus strains from 30 patients and 42 anti-HBe-positive asymptomatic carriers (ASCs) were characterized. G1896A pre-core stop mutants, detected in 77 % of e-CHB patients and 85 % of ASCs, showed no association with virus load or aminotransferase levels. Twenty per cent of e-CHB patients and 31 % of ASCs harboured T1762A1764 mutants. When this double mutation was associated with G1757, it was linked to a higher virus load in patients than when it was associated with A1757 (10(5.2+/-1.8) vs 10(3.2+/-0.8) copies ml(-1); P=0.004). Interestingly, the most common BCP mutations were T1764 and G1766, which were present in 33 % of e-CHB patients and 29 % of ASCs. These were associated with higher virus load and aminotransferase levels compared with patients lacking core promoter mutations, although this was not significant. The T1764G1766 double mutation was only present in strains with A1757 (P<0.001), which is more frequent in strains of genotype D than in those belonging to other genotypes. On the other hand, the T1762A1764 double mutation was found more frequently in association with G1757 than with A1757. The T1762A1764 double mutation forms a binding site for hepatocyte nuclear factor 1 (HNF1), which is constrained by A1757. However, the T1764G1766 double mutant may form a binding site for HNF3. Thus, position 1757 affects the emergence of promoter double mutants and would predict a relative genotypic restriction of both the T1762A1764 and the T1764G1766 double mutants.

Occult hepatitis B among chronic liver disease patients.

OBJECTIVE: Occult hepatitis B virus (HBV) infection is characterized by presence of HBV infection with undetectable hepatitis B surface antigen (HBsAg). Diagnosis of occult HBV infection requires sensitive HBV-DNA polymerase chain reaction (PCR) assay. Occult hepatitis B is a new entity and the prevalence of it and its clinical importance has not been investigated yet in Iran. The aim of this study is to investigate the prevalence and clinical importance of occult hepatitis B among chronic liver disease patients in Iran. METHODS: We studied 35 consecutive paraffin-embedded liver tissues cases referred to Research Center for Gastroenterology and Liver Diseases, Tehran, Iran during the year 2001 to 2002 for liver biopsy due to its elevation of alanine aminotransferase (ALT) levels for more than 6 months. Liver biopsies were reviewed and HBV-DNA and HBsAg and Hepatitis B core antigen were assayed in liver tissue by PCR and immunohistochemistry (IHC). RESULTS: Our patients with chronic liver disease (CLD) included hepatitis C (77.1%), cryptogenic liver disease (20%), and autoimmune hepatitis (2.9%). Histologically, chronic hepatitis, cirrhosis and non-specific changes were reported. Hepatitis B virus-DNA was detectable in 8 (22%) patients; however, IHC was negative in all. CONCLUSION: Occult hepatitis B is relatively frequent among patients with CLD in Iran. It maybe associated with more advanced liver pathology (cirrhosis) and more aggressive clinical course (decompensated cirrhosis). Occult HBV infection causes strong suppression of viral gene expression.

Hemochromatosis mutations in Iranians with hepatitis B virus infection.

In this study, the frequencies of the common hemochromatosis gene mutations were assessed in 75 Iranian subjects with chronic hepatitis B infection. We found that the major C282Y mutation was significantly more frequent in subjects infected with hepatitis B virus (4%) than in 194 control subjects (0%, P=.02; Fisher's exact test).