Polymorphisms of miR-146a and susceptibility to ulcerative colitis risk: a case-control study.

Considering the role of miR-146a in the control of inflammation, we assessed the importance of two miR-146a polymorphisms (rs2910164 and rs57095329) in the development and severity of ulcerative colitis (UC) in Iran. Genomic DNA of 150 cases with UC and 200 healthy individuals were genotyped using the PCR-RFLP technique. Statistical analyses were performed using Med Calc software. The miR-146a rs2910164 C allele was significantly associated with increased risk of UC. Individuals carrying the CC (rs2910164) were more than fourfold higher risk of UC relative to wild type homozygotes. The combined GC + CC genotypes were also associated with increased UC risk. We also found that the rs2910164 CC genotype was associated with a severe form of the disease However, the distribution of variant allele and genotypes of rs57095329 did not differ between the cases and controls. In conclusion, miR-146a rs2910164 polymorphism may play a role in UC. To confirm our findings, additional well-designed studies in diverse ethnic populations are required.

Detection of 23SrRNA Mutations Strongly Related to Clarithromycin Resistance in Helicobacter pylori Strains Isolated From Patients in the North of Iran.

BACKGROUND: Helicobacter pylori is curved Gram negative and microaerophilic bacilli that have infected half of the world's population. It is recognized as the causative agent of duodenal ulcer, gastritis peptic ulcer, mucosa-associated lymphoid tissue (MALT) lymphoma and is associated with gastric adenocarcinoma. Resistance to clarithromycin is related to point mutations in 23SrRNA gene on nt 2143 and 2144, when A turns to G, and A2143G is the most important type. These mutations lead to reduced affinity of antibiotics to their ribosomal target and are considered as the main cause of treatment failure. OBJECTIVES: The aim of this study was to determine the frequency of A2143G point mutation in 23SrRNA of H. pylori strains isolated from gastric biopsies of patients in Rasht, north of Iran, by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). PATIENTS AND METHODS: A descriptive study was performed on 89 H. pylori strains, which were isolated from gastric biopsies of patients with gastric disorders such as gastritis, peptic ulcer, duodenal ulcer, non-ulcer dyspepsia and gastric adenocarcinoma. Isolated strains were tested for clarithromycin resistance using as breakpoint a minimum inhibitory concentration (MIC) of ≥ 1 mg/L by the E-test. The presence of H. pylori DNA was confirmed by amplifying the ureC (glmM) gene by PCR. Also, point mutation on 23SrRNA gene (A2142G and A2143G) was detected by PCR-RFLP using MboII and BsaI restriction endonucleases in all extracted DNA. RESULTS: Of the 89 H. pylori isolates, eighty-four were susceptible to clarithromycin, while five (5.6%) were resistant. All DNA samples of resistant strains, which were treated with BsaI had A2143G mutation. There was no point mutation in the sensitive strains of H. pylori. Also, we detected no mutation on nt A2142G of resistant strains. CONCLUSIONS: In the present study, the frequency of clarithromycin resistance was lower than the other studies conducted in Iran. Resistance frequency in samples isolated from gastric ulcer was higher than other gastric disorders. Women and patients aged more than 60 years old showed the most resistance frequency in this study. All resistant strains had the A2143G genotype.

Epidemiologic Features of Inflammatory Bowel Disease in Guilan Province, North of Iran, During 2002-2012.

BACKGROUND The geographical incidence of IBD varies considerably. This study aimed to survey the epidemiologic features of IBD in Guilan province, North of Iran, during ten years duration. METHODS In this retrospective cross-sectional study, we assessed the documents of 868 patients with IBD referred to private and governmental clinics of Guilan province between 2002 and 2012. Variables such as demographic data, risk factors, diagnosis, extraintestinal manifestations and type of treatment were collected. RESULTS Among 868 patients with IBD, 756 patients (87.1%) diagnosed as UC and 112 patients (12.9%) as CD. The mean age of patients with UC and CD was 46.73±15.79 and 40.15±14.27 years respectively. Male/female ratio in UC and CD was 0.92:1 and 0.75:1 respectively. The most common age of disease initiation in UC was 40-59 years and in CD 20-39 years (p<0.001). Extraintestinal manifestations were seen in 25.4 percent of patients with IBD. Most of patients were treated with combination of two drugs: salicylates and azathioprine (p<0.04). The incidence of IBD gradually increased during the past 4 years in Guilan province. CONCLUSION This study showed that CD were presented significantly more common in younger patients than UC and totally the disease was slightly more common in female.

Effects of p53 codon 72 and MDM2 SNP309 polymorphisms on gastric cancer risk among the Iranian population.

BACKGROUND: Development of gastric cancer (GC) is a multistep process that requires alterations in the expression of oncogenes and tumor suppressor genes, occurring over several decades. The p53 tumor suppressor protein is involved in cell-cycle control, apoptosis and DNA repair. One of the most important regulators of p53 is MDM2, which acts as a negative regulator in the p53 pathway. Based on the key role of p53 and MDM2 in tumor suppression, polymorphisms that cause change in their function might affect cancer risk. We therefore elevated associations of the polymorphisms of p53 (R72P) and MDM2 (SNP309) with GC in Iran. MATERIALS AND METHODS: A total of 104 patients with gastric cancer and 100 controls were recruited. Genomic DNA was extracted from fresh gastric samples. Genotyping of the p53 and MDM2 genes was performed using allele specific PCR (AS-PCR). RESULTS: There was no significant difference between the p53 codon 72 polymorphism distribution in control and patient groups (p=0.54), but the G allele of MDM2 was found to be over-represented in patients (p=0. 01, Odds Ratio=2. 08, 95% Confidence Interval= 1.37-4.34). CONCLUSIONS: The p53 R72P seems not to be a potential risk factor for development of GC among Iranian patients, but our data suggest that MDM2 SNP309 might modify the risk related to GC.

Helicobacter pylori infection and MDM2 SNP309 association with gastric cancer susceptibility.

AIMS: MDM2 is a negative regulator of p53, and has also been implicated in carcinogenesis. The aim of this study was to define the causal association of Helicobacter pylori infection and the MDM2 SNP309 among northern Iranian patients with gastric cancer (GC). Two hundred and eight patients with GC and 200 cancer-free controls were genotyped for MDM2 SNP309 using the polymerase chain reaction-restriction fragment length polymorphism method. The ureC (glmM) gene was used for detection of H. pylori in this study. RESULTS: The G allele was found more frequently among patients with GC (55%) than among controls (37%). The risk of GC for MDM2 309G/G genotypes was considerably increased when compared with TT genotypes (odds ratio [OR]=15.93, 95% confidence interval [CI]=4.17-60.84). Among H. pylori-infected subjects, a significantly increased risk of GC associated with the GG genotype was quite clear (OR=14.66, 95% CI=3.54-60). CONCLUSIONS: The GG genotype was associated with an increased risk of gastric carcinoma. We also found that there is a joint effect of MDM2 SNP309G/G genotype and H. pylori infection for the development of gastric carcinoma. However, the findings need to be verified in large population-based prospective studies for more rigorous analyses of subgroups and gene-environment and gene-gene interactions.

Serum gastrin and the pepsinogen I/II ratio as markers for diagnosis of premalignant gastric lesions.

BACKGROUND: Iran is a country with very high incidences of stomach cancer, especially in Northern parts. Here we assessed prognostic value of serum screening biomarkers among people >50 years old for early detection of precancerous lesions in a hot spot for gastric carcinoma in Guilan Province, North Iran. METHODS: A cross- sectional population-based survey was conducted on 1,390 residents of Lashtenasha city with the mean age (SD) of 61.8 (9.02) years old (50.8% females) to assess the association of gastrin and the pepsinogen (PG) I/II ratio with premalignant gastric lesions. Blood samples were taken for CBC, blood group, and serologic exams (PGI, PGII, and gastrin 17) from each subject. Expert gastroenterologists performed upper GI endoscopy and ROC curves were generated to determine appropriate cutoff points. RESULTS: Mean values of PGI, PGII, PGI/PGII and gastrin were significantly different between patients with and without atrophy or metaplasia (P<0.05). To diagnose atrophy and intestinal metaplasia, a significantly higher AUC was observed for the PGI/PGII ratio (70 and 72%, respectively) compared to the PGI (56, 55%), PGII (63, 64%) and gastrin (59, 61%) (all p<0.001). CONCLUSIONS: Biomarker tests such as the PGI/II ratio can be used in the screening and diagnosis of subjects at high gastric cancer risk in our region.

Catalase gene C-262T polymorphism: importance in ulcerative colitis.

BACKGROUND AND AIM: Reactive oxygen species (ROS) are by-products of the cellular metabolism and have important roles in the normal physiology of the cell. However, when ROS production exceeds the antioxidant capacity, a state known as oxidative stress, damage to cellular macromolecules emerges. A crucial role in counteracting ROS is played by the enzyme catalase. A common polymorphism in the catalase (CAT) promoter region (C-262T) alters the expression as well as blood catalase levels, and leads to a number of human diseases. Ulcerative colitis (UC) is an inflammatory condition of the large bowel that is known to be influenced by oxidative stress. In this study, we aimed to evaluate the association of CAT C-262T polymorphism on the risk of UC. METHODS: Samples were collected from 60 patients diagnosed with UC and 78 control subjects, and genotyped by allele-specific polymerase chain reaction. RESULTS: We found that CAT C-262T genotype frequencies were significantly different between cases and controls (P = 0.002). Individuals carrying the -262C/T genotype had a greater risk for UC compared with C/C genotype (odds ratio, 4.88; 95% confidence interval, 1.73-13.75, P = 0.002). CONCLUSIONS: This study indicates that CAT C-262T polymorphism may be associated with UC, and that the -262C/T genotype may be a risk factor for the disease. Further studies are needed to confirm the results.

The Correlation between Microsatellite Instability and the Features of Sporadic Colorectal Cancer in the North Part of Iran.

Background. The aim of this study was to determine the correlation between MSI and sporadic colorectal cancer in Guilan province, North part of Iran. Materials and Methods. A total of 96 patients who underwent resection for sporadic colorectal cancer in Guilan province were studied. No patients had positive family history of cancers. The frequencies of MSI were analyzed by testing the BAT-26 and BAT-25 markers. Results. MSI analysis revealed that 22.9% of the tumors (22 patients) were microsatellite instability positive and 77.1% (74 patients) were microsatellite instability negative. The highest rate of MSI (40.9%) was found in the rectal region. MSI-H status was seen more frequently in distal tumors (P = 0.04, odds ratio = 3.13, 0.96-10.14). Conclusions. Distal tumor location and MSI may associate with special clinicopathological features. It seems that there may be correlation with underlying genetic and immunologic mechanisms.

Endoscopic findings in a mass screening program for gastric cancer in a high risk region - Guilan province of Iran.

BACKGROUND AND OBJECTIVES: Gastric cancer is a leading cause of cancer-related deaths in both sexes in Iran. This study was designed to assess upper GI endoscopic findings among people>50 years targeted in a mass screening program in a hot-point region. METHODS: Based on the pilot results in Guilan Cancer Registry study(GCRS), one of the high point regions for GC - Lashtenesha - was selected. The target population was called mainly using two methods: in rural regions, by house-house direct referral and in urban areas using public media. Upper GI endoscopy was performed by trained endoscopists. All participants underwent biopsies for rapid urea test (RUT) from the antrum and also further biopsies from five defined points of stomach for detection of precancerous lesions. In cases of visible gross lesions, more diagnostic biopsies were taken and submitted for histopathologic evaluation. RESULTS: Of 1,394 initial participants, finally 1,382 persons (702 women, 680 men) with a mean age of 61.7 ± 9.0 years (range:50-87 years) underwent upper GI endoscopy. H.pylori infection based on the RUT was positive in 66.6%. Gastric adenocarcinoma and squamous cell carcinoma of esophagus were detected in seven (0.5%) and one(0.07%) persons, respectively. A remarkable proportion of studied participants were found to have esophageal hiatal hernia(38.4%). Asymptomatic gastric masses found in 1.1% (15) of cases which were mostly located in antrum (33.3%), cardia (20.0%) and prepyloric area (20.0%). Gastric and duodenal ulcers were found in 5.9% (82) and 6.9% (96) of the screened population. CONCLUSION: Upper endoscopy screening is an effective technique for early detection of GC especially in high risk populations. Further studies are required to evaluate cost effectiveness, cost benefit and mortality and morbidity of this method among high and moderate risk population before recommending this method for GC surveillance program at the national level.

Living Fasciola hepatica in biliary tree: a case report.

Here we report a rare case of living Fasciola hepatica in biliary tract. The patient was in acute phase of infection and treated successfully with 10 mg/kg oral triclabendazole after the fluke was extracted using endoscopic retrograde cholangiopancreatography (ERCP).

Association of p53 codon 72 genetic polymorphism with the risk of ulcerative colitis in northern Iran.

PURPOSE: Ulcerative colitis (UC) is a chronic inflammatory condition of the large bowel of unknown etiology, characterized by the presence of bloody diarrhea and mucus associated with a negative stool culture for bacteria, ova, or parasites. The aim of this study was to investigate the association of p53 codon 72 genetic polymorphism with the risk of UC in northern Iran. METHODS: We evaluated the association of the p53 codon 72 genetic polymorphism with UC in northern Iran. The genotype of 190 patients with UC (115 men, 75 women; mean age, 32 ± 8.6 years) and 220 healthy control subjects (123 men, 97 women; mean age, 33 ± 2.5 years) were compared. Genomic DNA was extracted from colonic bioptic tissues of patients and blood samples of healthy individuals. Genotypes and allele frequencies were determined in patients and controls using allele-specific PCR (AS-PCR). RESULTS: There were significant differences in the distribution of the polymorphism between the control subjects and the UC patients (P < 0.0001). Significantly increased frequencies of the Pro allele and the Pro/Pro genotype were observed in patients with UC compared with controls (Pro allele: P < 0.0001; odds ratio, 7.87; 95% confidence interval, 4.03-15.35; Pro/Pro: P < 0.0001; odds ratio, 35.21; 95% confidence interval, 12.56-98.73). CONCLUSION: The p53 codon 72 genetic polymorphism is associated with UC in northern Iran.

Relationship between serum HBV DNA level and liver histology in HBV carriers with normal ALT in Guilan province, Iran.

BACKGROUND: Chronic hepatitis B virus (HBV) infection remains a major health problem. The aim of this study was to determine the serum HBV DNA levels in HBeAg-negative HBV patients and look for a relationship between serum HBV DNA level and liver histology. MATERIAL/METHODS: In a cross-sectional study, 70 patients with positive serum hepatitis B surface antigen (HBsAg) and normal ALT for at least 6 months were enrolled. Quantification of HBV DNA was performed by real-time PCR. Liver biopsy specimens were performed for grading and staging of chronic hepatitis. RESULTS: Fifty-four patients (34 males, 20 females) were included. Mean + or - SD serum HBV DNA level was 282,280.46 + or - 1,474,295 copies/ml, fibrosis (0-6) 2.37 + or - 1.263, necroinflammation (0-18) 0.33 + or - 0.476, and BMI 26.65 + or - 4.9. The mean serum HBV DNA level had significant differences between grade <4 and grade > or = 4 cases (P<0.05). The relationship between serum HBV DNA level and liver grade was confirmed by the Kendall test (P<0.05). No significant relationship between serum HBV DNA level and liver histological stage, gender, age, BMI, or HBeAg was observed in these patients (P>0.05). CONCLUSIONS: It is advantageous to measure serum HBV DNA level quantitatively in patients who are inactive carries of hepatitis B. If they have HBV DNA levels > or = 104 copies/ml, it will be necessary to perform a liver biopsy and apply therapy accordingly.

A randomized trial comparing four Helicobacter pylori eradication regimens: standard triple therapy, ciprofloxacin based triple therapy, quadruple and sequential therapy.

OBJECTIVE: Helicobacter pylori infection is found in at least 80% of people in developing countries. This randomized controlled trial was performed to evaluate the efficacy of 4 different H. pylori eradication regimens in Iranian patients. METHODS: We enrolled 428 patients referred to Razi hospital in Rasht city with dyspepsia. Patients were randomly assigned to four treatment groups of 107 patients (A-D). Group A received omeprazole, amoxicillin, metronidazole and bismuth, all given twice daily for 2 weeks. Group B received omeprazole, amoxicillin and clarithromycin, all given twice daily for 10 days. Group C patients were given omeprazole and amoxicillin, both twice daily for two weeks and ciprofloxacin twice a day for the first week. Group D received 10 days sequential treatment with omeprazole and amoxicillin for 5 days and omeprazole, clarithromycin and metronidazole all twice daily for the remaining 5 days. H. pylori status was rechecked by stool antigen test 8 weeks after treatment. H. pylori eradication rate (both "Intention to Treat" and "per Protocol") and adverse effects of the drugs were recorded after 8 weeks. RESULTS: Eradication rates in group A to D were, 84.1%, 90.7%, 65.4% and 80.4% respectively in "Intention to Treat" and 85.7%, 90.7%, 70%, and 81.1% respectively in "per Protocol" analyses. Patient compliance was significantly lower in Group C, whereas patient compliance in other groups was not significantly different. CONCLUSION: Standard 10 days triple therapy had the highest success (p=0.0001) rate in our study while quadruple therapy was the second successful regimen. Sequential therapy was not found to be an acceptable treatment option.

Immunogenicity of hepatitis B vaccine in multi-transfused thalassemic patients with and without hepatitis C infection: a comparative study with healthy controls.

BACKGROUND: Hepatitis C virus (HCV) infection is highly prevalent in thalassemic patients. This may decrease serum antibody response to hepatitis B virus (HBV) vaccine. There is also some alteration in the immune system of multi-transfused thalassemic patients as a consequence of iron overload. We deduced that HCV infection may reduce the effectiveness of HBV vaccine in multi-transfused thalassemic patients. MATERIAL/METHODS: Subjects were cited and studied prospectively in three groups. Group 1:125 multi-transfused thalassemic patients with negative serum HCV antibody, Group 2:96 multi-transfused thalassemic patients with positive serum HCV antibody on at least 2 different occasions, and Group3:100 healthy subjects. Subjects in all groups had negative serum HBsAg, anti-HBc, and anti-HBs, and they received three 20-microg doses of recombinant HBV vaccine in months 0,1, and 6. The anti-HBs titer was obtained one month after the last dose of vaccine and was considered seroprotective if > or =10 IU/l. RESULTS: The seroprotection rate was 83.2% in Group 1 and 80.2% in Group 2 (P = 0.74). It was 86% in healthy subjects, which didn't significantly differ from HCV-positive and -negative thalassemics (P = 0.56). Moreover, the mean values of ALT among the responder and non-responder thalassemic patients were 55.5 +/- 41.9 and 57.4 +/- 48.5 U/l, respectively (p = 0.802). During the vaccination periods, patients in all 3 groups did not show any significant adverse reactions. CONCLUSIONS: Our study shows that three standard doses of HBV vaccine are immunogenic and safe in multi-transfused thalassemic patients with or without HCV infection.