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Host Genetic Factors (host + genetic_factor)
Selected AbstractsInterleukin-2 Gene Polymorphisms Associated with Increased Risk of Gastric Atrophy from Helicobacter pylori InfectionHELICOBACTER, Issue 3 2005Shozo Togawa ABSTRACT Background., Gastric atrophy induced by Helicobacter pylori is thought to predispose patients to noncardiac gastric cancer development. However, the host genetic factors that influence the progression of gastric atrophy have not been elucidated. In this study, we examined the effects of cytokine polymorphisms on H. pylori -induced gastric atrophy. Methods., Blood samples were taken from 454 Japanese subjects. The interleukin-2 (IL-2; T-330G), IL-4 (C-33T), and IL-13 (C-1111T) polymorphisms were genotyped by polymerase chain reaction with confronting two-pair primers (PCR-CTPP). Anti- H. pylori IgG antibody and pepsinogen I and II were measured to diagnose H. pylori infection and atrophic gastritis. Results., The odds ratios (ORs) for the association between IL-2 polymorphism [OR = 2.78, 95% CI (confidence interval) = 1.26,6.17 (T/T to G/G)] or IL-4 polymorphism [OR = 2.22, 95% CI = 1.01,4.89 (T/C to C/C)] were increased significantly with gastric atrophy, whereas the corresponding OR of IL-13 polymorphism was decreased with gastric atrophy [OR = 0.61, 95% CI = 0.39,0.96 (C/T and T/T to C/C)]. There were no significant H. pylori seropositivity-related differences between these polymorphisms. We examined the relationship between these polymorphisms and gastric atrophy separately in H. pylori -seropositive and -seronegative groups. In the H. pylori -seropositive group, the IL-2 T/T (OR = 2.78, 95% CI = 1.12,6.93) had a significant association with gastric atrophy. Conclusions., These results reveal that the IL-2 gene polymorphism is associated with an increased risk of gastric atrophy induced by H. pylori infection and might predispose to gastric cancer. [source] Associations of HLA class II alleles with pulmonary tuberculosis in ThaisINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 5 2002S. Vejbaesya Summary Tuberculosis is an important infectious disease in Thailand. Susceptibility to tuberculosis is influenced not only by the environment but also by host genetic factors. In this study, we investigated HLA alleles in 82 patients with tuberculosis from Bangkok and in 160 normal controls. HLA-DRB1, DQA1 and DQB1 genotyping was performed by the PCR-SSO method. The frequency of HLA-DQB1*0502 was increased in tuberculosis patients compared to the normal controls (P = 0.01, OR = 2.06). In contrast, the frequencies of DQA1*0601 and DQB1*0301 were decreased in tuberculosis patients compared to the controls (P = 0.02 and P = 0.01, respectively). Our results suggest that HLA-DQB1*0502 may be involved in the development of pulmonary tuberculosis, whereas HLA-DQA1*0601 and DQB1*0301 may be associated with protection against tuberculosis. [source] Single nucleotide polymorphisms in the interferon-, and interleukin-10 genes do not influence chronic hepatitis C severity or T-cell reactivity to hepatitis C virusLIVER INTERNATIONAL, Issue 2 2004William G.H. Abbott Abstract: Background: The mechanisms by which interferon-, (IFN-,) contributes to inter-individual heterogeneity in the severity of chronic hepatitis C (CH-C) are unknown. In 116 consecutive patients with CH-C, we tested the hypothesis that host genetic factors regulating IFN-, production and activity influence the severity of liver damage and hepatitis C virus (HCV)-specific T-cell reactivity. Methods: We determined the genotypes of functionally significant polymorphisms in the IFN-, gene and in the promoter of interleukin-10 (IL-10), a cytokine that counteracts IFN-,. We also measured concanavalin A (Con A)-stimulated IL-10 and IFN-, production, and the frequency of virus-specific T-cells, producing IFN-, or IL-10. Results: The grade of inflammation and the stage of fibrosis of CH-C showed no associations with either the IFN-, or IL-10 promoter polymorphisms or with Con A-stimulated IL-10 or IFN-, production. Similarly, there were no associations between HCV-specific T-cell frequencies and these host genetic factors. On multivariate analysis, the grade of inflammation and the duration of HCV infection accounted for only 37% of the variance in the stage of CH-C (P<0.0001). This percentage did not increase by including any genetic variables in the analyses. Conclusion: Future studies investigating the entire cytokine gene sequences will provide better information regarding genetic variations responsible for inter-individual differences in the severity of CH-C. [source] Microarray analysis of gene expression associated with extrapulmonary dissemination of tuberculosisRESPIROLOGY, Issue 5 2006Deog Kyeom KIM Objective: Although extrapulmonary organs are involved in 20% of patients with tuberculosis, the host genetic factors associated with the extrapulmonary dissemination of tuberculosis are not yet known. The aim of this study was to identify the host genetic factors associated with the extrapulmonary dissemination of tuberculosis by comparing gene expression profiles of patients who had recovered from extrapulmonary tuberculosis and those who had recovered from pulmonary tuberculosis. Methods: Five patients from each group were enrolled. Total RNA was extracted from peripheral blood mononuclear cells that had been incubated for 48 h with whole lysate of Mycobacterium tuberculosis (H37Rv, 0.5 µg/mL). Gene expression profiles were acquired using the GeneChip® array and its applied systems. Gene expression profiles from five patients with previous extrapulmonary tuberculosis and one pooled control sample from five patients with previous pulmonary tuberculosis were analysed and compared. Genes that were expressed concordantly in more than 80% of arrays and that showed more than twofold changes in at least one array among samples from patients who had recovered from extrapulmonary tuberculosis were identified. Results: Compared with the control sample, the expression of 16 genes, including those for tumour necrosis factor (TNF)-, and cathepsin W, was increased, and the expression of 45 genes including that for TNF-receptor superfamily member 7 (TNFRSF7), was decreased in the extrapulmonary tuberculosis patients. The altered expression of the TNF-,, cathepsin W and TNFRSF7 genes was confirmed by quantitative RT-PCR. Conclusions: Altered expression of the genes for TNF-,, cathepsin W and TNFRSF7 may be risk factors for the extrapulmonary dissemination of tuberculosis in humans. [source] Do helminth parasites protect against atopy and allergic disease?CLINICAL & EXPERIMENTAL ALLERGY, Issue 1 2009C. Flohr Summary Allergic diseases are rare in areas with high helminth parasite exposure and common where helminth exposure is lacking or significantly reduced, such as urban areas of developing countries and industrialized nations. Studies suggest that helminths induce a systemic immuno-modulatory network, including regulatory T cells and anti-inflammatory IL-10, which might play a key role in the protection against the allergic phenotype. Here, we review the current cross-sectional, birth cohort, and intervention study evidence for a protective effect of helminth infection on allergy. There is increasing evidence for a causal relationship between helminth infection and reduced skin prick test responsiveness to allergens. Cross-sectional studies have shown a consistent negative relationship, and these results have been confirmed in several, although not all, intervention studies. The immunological basis for this protective effect is less clear. Recent studies do not support the mast-cell IgE saturation hypothesis, but suggest that protection is associated with IL-10 production. As for allergic disease, cross-sectional studies support a negative relationship between clinical asthma and infection with some helminth species, particularly hookworm, but more studies are required to draw conclusions for eczema and rhinitis. In addition, none of the few intervention studies to date have demonstrated an increase in clinical allergy after helminth treatment, and further studies are needed. Furthermore, we are only beginning to understand the host genetic factors that are potentially involved. A genetically predetermined T-helper type 2 cell-dominated cytokine milieu reduces parasite burden and may enhance host survival in an environment where helminth parasites are prevalent. Lack of parasite exposure in such hosts might lead to hypersensitivity to seemingly minor environmental allergen stimuli. Large birth cohort studies in helminth-endemic areas that use epidemiological, genetic, and immunological tools are required to further examine how helminth parasites affect the development of atopy and allergic disease. Intervention studies with hookworm in parasite-naïve allergic individuals are currently ongoing in the United Kingdom to test the above hypotheses further. [source] | ||||||||||