ATP binding cassette and cholecystokinin A receptor genetic variations in gallstone susceptibility.

AIM: It was aimed to assess the association of four polymorphisms and relative haplotypes in the ATP binding cassettes and cholecystokinin A receptor (rs6720173, rs11887534, rs4148217, rs1800857) with the risk of gallstone. BACKGROUND: Gallstone is a multifactorial disease. Besides high penetrance genes, low or moderate penetrance polymorphisms may increase susceptibility to gallstone. METHODS: 200 gallstone patients and 251 healthy controls were analyzed in a case-control association model. Genotyping was carried out by restriction fragment length polymorphism. Randomly 10% of samples underwent for direct sequencing to confirm results. RESULTS: Heterozygote variant of rs11887534 demonstrated protective effect on the risk of gallstone susceptibility in males (P=0.013; OR=0.125; CI95%=0.048-0.325). In contrast, C/C genotype associated with gallstone susceptibility in females (P=0.004; OR=5.555 CI95%=1.975-10.632). Moreover, rs1800857 showed association only in females (P=0.019; OR=0.283; CI95%=0.099-0.811). Haplotype analysis for rs1800857 showed GC, CC and CA association with gallstone. CONCLUSION: The most imperative polymorphisms of contributing genes to gallstone were analyzed in this study and rs11887534 and rs1800857 appeared to be associated with gallstone, which is expected to be further verified in a larger cohort in the future.

The Early Results of a New Health Care Program Implementation in HBV Screening: an Iranian Experience.

BACKGROUND According to the reports of World Health Organization (WHO) and Centers for Disease Control and Prevention, the prevalence of chronic hepatitis B infection in Iran has decreased from 2-7% in 2001 to 1.3-0.8% in children aged 2-14 years. In 2010 the Institute of Medicine recommended more comprehensive screening by primary care physicians (PCPs) for evaluation, vaccination, and management of infected patients for further decrease in the prevalence of chronic HBV infection. Thus, with contribution of the Health Department, we developed a practical flowchart for PCPs to start active screening of hepatitis B virus (HBV) in all visited patients and refer the positive cases for further evaluation and management to Taleghani Hospital. METHODS With collaboration of Health Department of Shahid Beheshti University of Medical Sciences), physicians of health centers were asked to screen all their patients for HBsAg. Positive cases were referred to Taleghani Hospital. They were first registered and educated about their disease, life style, and prevention methods. Their first degree families were screened for HBV infection too and were referred for vaccination if needed. According to the results of lab tests, appropriate management was done by a hepatologist. RESULTS Since implementation of this program, we have encountered a significant rise in patient detection (even in high risk groups). Many of them were not aware of their disease and most of those who were aware of their disease were not managed appropriately. Family screening and vaccination were inadequate and need more emphasis. CONCLUSION Although health system is active about screening of HBV infection in high risk populations, it is not perfect. It seems that health system needs to upgrade the screening and management programs of HBV infection.

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.

Phylogenetic analysis of hepatitis C virus strains and risk factors associated with infection and viral subtypes among Iranian patients.

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.

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].

Interleukin-16 gene polymorphisms are considerable host genetic factors for patients' susceptibility to chronic hepatitis B infection.

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.

Correlation between the EGF gene intronic polymorphism, rs2298979, and colorectal cancer.

Colorectal cancer (CRC) is an important disorder that results from genetic and epigenetic alterations in one colonic epithelial cell. Epidermal growth factor (EGF) is critical in the development of tumors in epithelial tissues. Variations in the DNA sequence of the EGF gene may be particularly significant with regard to susceptibility to CRC. The present study aimed to investigate the effect of the EGF gene single nucleotide polymorphism (SNP), rs2298979, on CRC. In this prospective study, 220 samples were collected from patients with CRC and compared with 220 matched healthy controls. Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, and the result was validated by direct sequencing. A significant correlation was observed between the rs2298979 variant in the EGF gene and CRC. The frequency of the A/G genotype in the control group was higher than in the patients with sporadic CRC [odds ratio (OR), 0.488; 95% confidence interval (CI), 0.307-0.774; P=0.002]. In this study there were no individuals with a G/G genotype. Although the frequency of the G and A alleles was similar in the healthy control and CRC patient groups, individuals with the A/G genotype were less susceptible to CRC compared with those with the A/A genotype.

Association of co-stimulatory human B-lymphocyte antigen B7-2 (CD86) gene polymorphism with colorectal cancer risk.

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.

Detection of human Bocavirus 1, 2 and 3 from patients with acute gastroenteritis.

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.

Molecular analysis of imperative polymorphisms of MLH1 gene in sporadic colorectal cancer.

BACKGROUND: Single nucleotide polymorphisms in mismatch repair genes may be associated with different protein expression, production, and efficiency according to allele status and influence the risk of developing colorectal cancer. OBJECTIVE: This research aimed at analyzing two important polymorphisms in MLH1 gene and their association in colorectal cancer susceptibility. METHODS: In total, 219 CRC patients and 248 healthy controls were genotyped with PCR/RFLP for I219V and IVS12-169 C>T polymorphisms in MLH1 gene. Sequencing performed to ensure work flow and results. We used unconditional logistic regression after adjusting for age and sex to evaluate the association between each polymorphism and colorectal cancer. RESULTS: The MLH1 I219V polymorphism was associated with colorectal cancer susceptibility (P=0.01). Stratified data analysis for gender demonstrated association of AG (P=0.009) and GG (P=0.021) genotypes with risk of colorectal cancer in women. In contrast there is no association with IVS 12-169 C>T polymorphism and colorectal cancer risk. CONCLUSIONS: I219V SNP might be a susceptibility factor for CRC and gender is a factor that must be considered when it is analyzing. Further tests need to be done to define it as a dependable prognosis factor.