Interleukin-6-174G/C polymorphism is associated with a decreased risk of type 2 diabetes in patients with chronic hepatitis C virus.

BACKGROUND: Chronic hepatitis C (CHC) is associated with type 2 diabetes mellitus. Although the pathogenesis remains to be elucidated, a growing evidence has suggested a role of pro-inflammatory immune response. Increased serum concentrations of Interleukin 6 (IL-6) have been associated with insulin resistance, type 2 diabetes mellitus as well as advanced forms of liver disease in chronic hepatitis C infection. AIM: To investigate the frequency of IL-6-174G/C (rs1800795) single nucleotide polymorphism (SNP) in CHC patients and in healthy subjects of the same ethnicity. Associations between type 2 diabetes mellitus (dependent variable) and demographic, clinical, nutritional, virological and, IL-6 genotyping data were also investigated in CHC patients. METHODS: Two hundred and forty-five patients with CHC and 179 healthy control subjects (blood donors) were prospectively included. Type 2 diabetes mellitus was diagnosed according to the criteria of the American Diabetes Association. Clinical, biochemical, histological and radiological methods were used for the diagnosis of the liver disease. IL-6 polymorphism was evaluated by Taqman SNP genotyping assay. The data were analysed by logistic regression models. RESULTS: Type 2 diabetes mellitus, blood hypertension and liver cirrhosis were observed in 20.8% (51/245), 40.0% (98/245) and 38.4% (94/245) of the patients, respectively. The frequency of the studied IL-6 SNP did not differ between the CHC patients and controls (P = 0.81) and all alleles were in Hardy-Weinberg equilibrium (P = 0.38). In the multivariate analysis, type 2 diabetes mellitus was inversely associated with GC and CC genotypes of IL-6-174 (OR = 0.42; 95%CI = 0.22-0.78; P = 0.006) and positively associated with blood hypertension (OR = 5.56; 95%CI = 2.79-11.09; P < 0.001). CONCLUSION: This study was the first to show that GC and CC genotypes of IL-6-174 SNP are associated with a decreased risk of type 2 diabetes mellitus in patients chronically infected with hepatitis C virus. The identification of potential inflammatory mediators involved in the crosstalk between hepatitis C virus and the axis pancreas-liver remains important issues that deserve further investigations.

The combined polymorphisms of interleukin-6-174GG genotype and interleukin-10 ATA haplotype are associated with a poor quality of life in patients with chronic hepatitis C.

PURPOSE: Chronic hepatitis C (CHC) is associated with a decreased health-related quality of life (HRQOL). More recent studies have pointed toward a genetic basis of patient-reported quality of life outcomes. Taking into account that the influence of single-nucleotide polymorphisms (SNPs) on the HRQOL of CHC patients has not been studied, we investigated the combined IL10-1082G/A, - 819C/T, and - 592C/A SNPs, and IL6-174G/C SNP. We also evaluated the association between demographic, clinical, psychiatric, virological, and genetic variables with domains and summaries of HRQOL in CHC patients. METHODS: 132 consecutive CHC patients and 98 controls underwent psychiatric evaluation by using the Mini International Neuropsychiatric Interview. HRQOL was assessed by a generic questionnaire, the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), and by the specific Liver Disease Quality of Life Questionnaire (LDQOL). IL6 and IL10 polymorphisms were evaluated by Taqman SNP genotyping assay. Multivariate analysis was used to evaluate the associations. RESULTS: Major depressive disorder was associated with lower SF-36 and LDQOL scores in seven and ten domains, respectively. Diabetes and hypertension were also associated with reduced HRQOL. CHC patients carrying the combination of IL10 ATA haplotype/IL6-GG genotype had lower scores in the SF-36-physical functioning domain, and reduced scores in the LDQOL effects of liver disease on activities of daily living, quality of social interaction, and sexual function domains than the non-carriers of the combined haplotype/genotype. CONCLUSION: This is the first study to demonstrate that combined IL6 high-producer GG genotype and IL10 low-producer ATA haplotype is associated with poorer HRQOL in CHC patients.

oipA "on" status of Helicobacter pylori is associated with gastric cancer in North-Eastern Brazil.

BACKGROUND: Although, outer membrane protein OipA of Helicobacter pylori has been associated with gastric mucosal damage and gastroduodenal diseases, studies evaluating gastric cancer patients are scarce. We investigated whether the functional oipA "on" status was associated with gastric cancer in the North-eastern Brazil, region with high prevalence of gastric cancer. METHODS: We included samples from 95 H. pylori positive subjects (23 patients with gastritis, 24 with gastric cancer, 32 first-degree relatives of gastric cancer patients and 16 children). oipA was assayed by polymerase chain reaction (PCR) and DNA sequencing. cagA and vacA status were evaluated by PCR. RESULTS: Overall 81.1% of the H. pylori strains had functional oipA. In adults, the oipA "on" status (OR = 9.20; 95%CI = 1.45-58.48, P = 0.02) and increasing age (OR = 1.08; 95%CI = 1.03-1.14; P = 0.003) were independently associated with gastric cancer in a logistic model. The oipA "on" status (OR = 14.75; 95%CI: 2.53-86.13, P = 0.003) was also associated with first-degree relatives of gastric cancer patients when compared with gastritis. The frequency of oipA "on" status did not differ between children and adults (P = 0.87). The oipA "on" status was significantly correlated with the presence of cagA and vacA s1 m1. CONCLUSION: oipA "on" status was independently associated with gastric cancer and first-degree relatives of gastric cancer patients in North-eastern Brazil.

Interleukin-10 promoter gene polymorphisms are associated with the first major depressive episode in chronic hepatitis C patients.

AIMS: To investigate the association of IL10 SNPs in chronic hepatitis C (CHC) patients with and without the first major depressive episode (MDE), as well as their association with plasma levels of target cytokines. METHODS: A hundred and thirty two CHC patients (32 with and 100 without first MDE) and 98 controls were prospectively enrolled in this cross-sectional study. MDE was diagnosed by a psychiatrist, using the Mini International Neuropsychiatric Interview Plus 5.0. IL10 polymorphisms (-1082 G/A, -819C/T and -592C/A IL10 SNPs) were evaluated by Taqman SNP genotyping assay. Plasma concentrations of IL-2, IL-6, IL-10, IFN-γ and TNF-α were determined using the Human Th1/Th2 Cytometric Bead Array kit. The associations were investigated by logistic models. RESULTS: The frequencies of the studied IL10 SNPs did not differ between the CHC patients and controls. The first MDE was positive and independently associated with the IL10-1082*A, IL10-819*T and IL10-592*A (ATA) low producer haplotype (OR = 1.50; 95% CI = 1.11-2.04; P = 0.009) and current alcohol misuse (OR = 4.29; 95% CI = 1.22-15.05; P = 0.02), and inversely associated with increasing age (OR = 0.94; 95% CI = 0.91-0.98; P = 0.006). In addition, plasma level of TNF-α was significantly higher in the carriers than in the non-carriers of the IL10 ATA haplotype in patients with the first MDE. The IL-10 and IL-2 plasma levels were significantly higher in the carriers than in non-carriers of the IL10 GCC high producer haplotype, demonstrating the functionality of the studied IL10 polymorphisms. CONCLUSIONS: This is the first study to demonstrate that the IL10 low producer ATA haplotype is associated with the first MDE in patients with CHC.

CagA-positive Helicobacter pylori strain containing three EPIYA C phosphorylation sites produces increase of G cell and decrease of D cell in experimentally infected gerbils (Meriones unguiculatus).

PURPOSE: Human infection by Helicobacter pylori is associated with an increase in the number of gastrin-producing G cells and a concomitant decrease of somatostatin-producing D cells. However, to our knowledge, changes in G and D cell numbers in response to infection with H. pylori CagA-positive strains containing different number of EPIYA-C phosphorylation sites have not been analyzed to date. Therefore, the aim of this study was to perform a quantitative analysis of the number of G and D cells in Mongolian gerbils challenged with H. pylori strains with different numbers of EPIYA-C motifs. MATERIALS AND METHODS: Mongolian gerbils were inoculated with isogenic H. pylori strains containing one to three phosphorylation sites. Mucosal fragments were evaluated by morphometry and immunohistochemistry using primary polyclonal rabbit anti-gastrin and anti-somatostatin antibodies. Positive cells were counted using an image analyzer. RESULTS: Forty-five days after infection, there was a decrease in the number of D cells and an increase in the G/D cell ratio in the group with three EPIYA-C. Six months after infection, there was a progressive and significant increase in the number of G cells and in the G/D cell ratio, with a concomitant decrease in the number of D cells, especially in the three EPIYA-C group. CONCLUSIONS: CagA-positive H. pylori strains containing a large number of EPIYA-C phosphorylation sites induce a decrease in D cell number and an increase in G cell number and G/D ratio, which were correlated with the number of inflammatory cells of the lamina propria.

CagA phosphorylation EPIYA-C motifs and the vacA i genotype in Helicobacter pylori strains of asymptomatic children from a high-risk gastric cancer area in northeastern Brazil.

Helicobacter pylori infection is one of the most common infections worldwide and is associated with gastric diseases. Virulence factors such as VacA and CagA have been shown to increase the risk of these diseases. Studies have suggested a causal role of CagA EPIYA-C in gastric carcinogenesis and this factor has been shown to be geographically diverse. We investigated the number of CagA EPIYA motifs and the vacA i genotypes in H. pylori strains from asymptomatic children. We included samples from 40 infected children (18 females and 22 males), extracted DNA directly from the gastric mucus/juice (obtained using the string procedure) and analysed the DNA using polymerase chain reaction and DNA sequencing. The vacA i1 genotype was present in 30 (75%) samples, the i2 allele was present in nine (22.5%) samples and both alleles were present in one (2.5%) sample. The cagA-positive samples showed distinct patterns in the 3’ variable region of cagA and 18 of the 30 (60%) strains contained 1 EPIYA-C motif, whereas 12 (40%) strains contained two EPIYA-C motifs. We confirmed that the studied population was colonised early by the most virulent H. pylori strains, as demonstrated by the high frequency of the vacA i1 allele and the high number of EPIYA-C motifs. Therefore, asymptomatic children from an urban community in Fortaleza in northeastern Brazil are frequently colonised with the most virulent H. pylori strains.

CagA phosphorylation EPIYA-C motifs and the vacA i genotype in Helicobacter pylori strains of asymptomatic children from a high-risk gastric cancer area in northeastern Brazil

Helicobacter pylori infection is one of the most common infections worldwide and is associated with gastric diseases. Virulence factors such as VacA and CagA have been shown to increase the risk of these diseases. Studies have suggested a causal role of CagA EPIYA-C in gastric carcinogenesis and this factor has been shown to be geographically diverse. We investigated the number of CagA EPIYA motifs and the vacA i genotypes in H. pylori strains from asymptomatic children. We included samples from 40 infected children (18 females and 22 males), extracted DNA directly from the gastric mucus/juice (obtained using the string procedure) and analysed the DNA using polymerase chain reaction and DNA sequencing. The vacA i1 genotype was present in 30 (75%) samples, the i2 allele was present in nine (22.5%) samples and both alleles were present in one (2.5%) sample. The cagA-positive samples showed distinct patterns in the 3’ variable region of cagA and 18 of the 30 (60%) strains contained 1 EPIYA-C motif, whereas 12 (40%) strains contained two EPIYA-C motifs. We confirmed that the studied population was colonised early by the most virulent H. pylori strains, as demonstrated by the high frequency of the vacA i1 allele and the high number of EPIYA-C motifs. Therefore, asymptomatic children from an urban community in Fortaleza in northeastern Brazil are frequently colonised with the most virulent H. pylori strains. .