Extracellular matrix protein 1 gene rs3737240 single nucleotide polymorphism is associated with ulcerative colitis in Turkish patients.

BACKGROUND/AIMS: Ulcerative colitis (UC) and Crohn's disease are chronic inflammatory diseases. Genetic, immunologic, and microbial factors play an important role in their pathogenesis. Extracellular matrix protein 1 (ECM1), a gene related to mucosal barrier function, has been shown to be associated with UC. This study aims to determine the relationship between ECM1 gene rs3737240 single nucleotide polymorphism (SNP) and UC in a group of Turkish patients. MATERIALS AND METHODS: Ninety-four UC patients and 120 healthy controls were enrolled in the study. ECM1 gene rs3737240 SNP genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: TT genotype was significantly more common in UC patients than in the healthy control group [p=0.034; odds ratio (OR) 2.34; 95% confidence interval (CI) 1.04-5.25]. The presence of C allele significantly lowered the UC risk (p=0.034; OR 0.42; 95% CI 0.19-0.95). TT genotype was significantly associated with azathioprine use in UC patients (p=0.037; OR 3.0; 95% CI 1.04-8.65). The C allele significantly reduced the probability of azathioprine use in UC patients (p=0.037; OR 0.33 CI 95% 0.11-0.96). No relation was found between rs3737240 SNP genotype and the phenotypical characteristics of UC patients. CONCLUSION: The TT genotype of ECM1 gene rs3737240 SNP significantly increased susceptibility for UC and azathioprine use in UC patients in a Turkish population.

Therapeutic success with bismuth-containing sequential and quadruple regimens in Helicobacter pylori eradication.

BACKGROUND AND STUDY AIMS: The success rate of Helicobacter pylori (H. pylori) eradication with the classical triple therapy is gradually declining. In this study, we aimed to compare and assess the efficacies of six different eradication regimens including sequential protocols. PATIENTS AND METHODS: Endoscopically confirmed nonulcer dyspepsia patients were enrolled. H. pylori presence was determined either histologically or by a rapid urease test. Treatment-naive patients were randomly assigned to an either one of three 10-day (OAC, OTMB, and OACB) or one of three sequential protocols (OA+OCM, OA+OCMB, and OA+OMDB) (O=omeprazole, A=amoxicillin, C=clarithromycin, T=tetracycline, M=metronidazole, B=bismuth, D=doxycycline). The eradication was assessed 6-8weeks after the completion of the treatment by a 14C-urea breath test. RESULTS: In total, 301 patients were included. Fifty-two percent of the participants (n=157) were female, and the mean age was 44.9years (range=18-70). The intention to treat (ITT) and per protocol (PP) eradication rate for each regimen is as follows: OAC (ITT=61.2%, PP=75%), OTMB (83.3%, 87%), OACB (76.5%, 79.6%), OA+OCM (72.3%, 73.9%), OA+OCMB (82.7%, 89.6%), and OA+OMDB (59.3%, 65.3%). Smoking significantly affected the eradication rate (P=0.04). CONCLUSION: In this study, OTMB and OA+OCMB were significantly superior to the triple therapy and succeeded to reach the eradication rate proposed by the Maastricht consensus (over 80%). These two bismuth-containing regimens could be considered for first-line therapy in the regions with high clarithromycin resistance.

HLA DPB1 15:01 Allele Predicts Spontaneus Hepatitis B Surface Antigen Seroconversion.

AIM: Chronic hepatitis B (CHB) is a global health problem. Recent genome-wide association studies (GWAS) exposed signifi-cant association between the human leukocyte antigen (HLA) class II region, including both DP and DQ loci, and chronic hepatitis B. Previous research also indicated the involvement of adaptive immune system in Hepatitis B seroconversion. The aim of this study is to investigate possible polymorphisms in the HLA-DP locus that can contribute to immune response to Hepatitis B virus (HBV). METHODS: We enrolled 94 chronic hepatitis B (CHB) patients and a control group of 85 spontaneous seroconverted healthy subjects and genotyped HLA-DPB1 alleles by polymerase chain reaction followed by restriction length polymorphism (PCR-RFLP) and Sanger sequencing. RESULTS: Among the 19 DPB1 alleles analyzed in this study, DPB1*15:01 allele was more frequent in the spontaneous sero-converted control group compared to CHB patients (15.3% vs. 1.1%, χ2 = 12.5, OR = 0.06, 95% CI = 0.08-0.046 P < 0.001, Pcorrected < 0.001). DPB1*02:01 and DPB1*10:01 were the other alleles observed more frequently in the control group (38.8% vs. 22.3% P = 0.02 and 16.5% vs. 5.3% P = 0.02, respectively). However associations of these two alleles were lost their significance after Bonferoni's correction (Pcorrected = 0.4 for all). CONCLUSIONS: In conclusion, this study demonstrates that HLA alleles may participate in spontaneous HBsAg seroconversion which is the ultimate target in CHB in Turkish CHB patients.

A potential treatment of non-alcoholic fatty liver disease with SIRT1 activators.

Sirtuins (SIRTs) are members of the silent information regulator-2 family and act as nicotinamide adenine dinucleotide (NAD+)-dependent histone/protein deacetylases. The de-acetylation of proteins and histones results in an up- or down-regulation of gene transcription and protein function. In recent years, the regulatory action of the deacetylation activity of SIRT1 has been shown to have a positive impact on the pathophysiological mechanisms of nonalcoholic fatty liver disease (NAFLD). Among the effects of SIRT1 are: its healing activity on insulin sensitivity, thereby ameliorating glycemic regulation; its mimetic activity on calorie restriction; its antihyperlipidemic activity on lipid homeostasis via the liver, adipose tissues and skeletal muscles; its anti-inflammatory activities; its protective effects against cardiovascular events and endothelial dysfunction; its positive influence on autophagy, apoptosis and cancer; and finally, its anti-aging activity. The current approach for the treatment of NAFLD involves the treatment of etiological factors and recommendation of life-style changes including more physical activity and a low-calorie diet. However, there is no specific medical treatments for NAFLD. The therapeutic potential of SIRT1 activity in the treatment of NAFLD discovered in humans has been presented in this article. In this review, the potential effects of SIRT1 activation on NAFLD-related pathophysiological mechanisms and on the treatment of NAFLD are discussed.

Association of human leukocyte antigen DQB1 and DRB1 alleles with chronic hepatitis B.

AIM: To investigate the effect of human leukocyte antigen (HLA) DRB1 and DQB1 alleles on the inactive and advanced stages of chronic hepatitis B. METHODS: Patient records at a single institution's hepatology clinic were reviewed. Demographic data, laboratory results, endoscopy results, virological parameters, biopsy scores and treatment statuses were recorded. In total, 355 patients were eligible for the study, of whom 226 (63.7%) were male. Overall, 82 (23.1%) were hepatitis B early antigen (HBeAg) positive, 87 (24.5%) had cirrhosis, and 66 (18.6%) had inactive disease. The presence of DQB1 and DRB1 alleles was determined by polymerase chain reaction with sequence-specific primers. The distribution of the genotyped alleles among patients with cirrhosis and patients with chronic active hepatitis was analyzed. RESULTS: The most frequent HLA DQB1 allele was DQB1*03:01 (48.2%), and the most frequent HLA DRB1 allele was DRB1*13/14 (51.8%). DQB1*05:01 was more frequent in patients with active disease than in inactive patients (27% vs 9.1%; P = 0.002, Pc = 0.026). DRB1*07 was rare in patients with cirrhosis compared with non-cirrhotics (3.4% vs 16%; P = 0.002, Pc = 0.022). Older age (P < 0.001) and male gender (P = 0.008) were the other factors that affected the presence of cirrhosis. In a multivariate logistic regression analysis, DRB1*07 remained a significant negative predictor of cirrhosis (P = 0.015). A bioinformatics analysis revealed that a polymorphic amino acid sequence in DRB1*07 may alter interaction with the T-cell recognition site. CONCLUSION: This study demonstrates that HLA alleles may influence cirrhosis development and disease activity in Turkish chronic hepatitis B patients.

Serum concentrations of human insulin-like growth factor-1 and levels of insulin-like growth factor-binding protein-5 in patients with nonalcoholic fatty liver disease: association with liver histology.

OBJECTIVE: In this study, we aimed to investigate the relationship between the histological features of nonalcoholic fatty liver disease (NAFLD) and serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-5 (IGFBP-5) to determine the usefulness of this relationship in clinical practice. MATERIALS AND METHODS: Serum samples were collected from 92 patients with biopsy-proven NAFLD and 51 healthy controls and serum levels of IGF-1 and IGFBP-5 were assayed by enzyme-linked immunosorbent assay. RESULT: Serum IGFBP-5 levels were correlated with liver steatosis, fibrosis, and nonalcoholic steatohepatitis scores. IGF-1 levels were significantly decreased in patients with moderate-to-severe fibrosis compared with patients with no or mild fibrosis. CONCLUSION: Serum IGFBP-5 levels may be useful to differentiate both advanced fibrosis and definite nonalcoholic steatohepatitis from other NAFLD groups. Also, serum IGF-1 levels may be useful to differentiate advanced fibrosis in patients with NAFLD.