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      Genetic Polymorphisms of Molecules Associated with Innate Immune Responses, TRL2 and MBL2 Genes in Japanese Subjects with Functional Dyspepsia

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          Abstract

          Inflammatory changes in the gastric mucosa are commonly observed in Japanese patients with functional dyspepsia (FD). However, detailed data regarding the possible association between the genetic factors of inflammation related molecules and FD are not available. Toll like receptor 2 (TLR2) and mannan-binding lectin (MBL) protein play important roles in the innate immune activation. We aimed to clarify the association between common polymorphisms of TLR2 and MBL2 genes with FD in Japanese subjects. TLR2 −196 to −174 del and MBL2 codon54 G/A polymorphisms were genotyped in 111 FD patients according to Rome III criteria and 106 asymptomatic controls. Non-significant correlation was found between TLR2 and MBL2 polymorphisms with FD. However, in Helicobacter pylori ( H. pylori) positives, we found significant inverse association between TLR2 −196 to −174 del carrier and FD among H. pylori positive subjects (Adjusted odds ratio (OR) = 0.48, 95% confidence interval (CI) = 0.23–0.996, p = 0.0488). We also found significant inverse association between the same genotype with postprandial distress syndrome (PDS) among H. pylori positive subjects (Adjusted OR = 0.22, 95% CI = 0.07–0.69, p = 0.0099). Our data suggest that TLR2 −196 to −174 del carriers’s status but not MBL2 codon54 G/A is inversely related to the risk with FD in H. pylori-infected subjects.

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          Most cited references37

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          Toll-like receptors: critical proteins linking innate and acquired immunity.

          Recognition of pathogens is mediated by a set of germline-encoded receptors that are referred to as pattern-recognition receptors (PRRs). These receptors recognize conserved molecular patterns (pathogen-associated molecular patterns), which are shared by large groups of microorganisms. Toll-like receptors (TLRs) function as the PRRs in mammals and play an essential role in the recognition of microbial components. The TLRs may also recognize endogenous ligands induced during the inflammatory response. Similar cytoplasmic domains allow TLRs to use the same signaling molecules used by the interleukin 1 receptors (IL-1Rs): these include MyD88, IL-1R--associated protein kinase and tumor necrosis factor receptor--activated factor 6. However, evidence is accumulating that the signaling pathways associated with each TLR are not identical and may, therefore, result in different biological responses.
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            Toll-like receptors control activation of adaptive immune responses.

            Mechanisms that control the activation of antigen-specific immune responses in vivo are poorly understood. It has been suggested that the initiation of adaptive immune responses is controlled by innate immune recognition. Mammalian Toll-like receptors play an essential role in innate immunity by recognizing conserved pathogen-associated molecular patterns and initiating the activation of NF-kappaB and other signaling pathways through the adapter protein, MyD88. Here we show that MyD88-deficient mice have a profound defect in the activation of antigen-specific T helper type 1 (TH1) but not TH2 immune responses. These results suggest that distinct pathways of the innate immune system control activation of the two effector arms of adaptive immunity.
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              Evolution of the lectin-complement pathway and its role in innate immunity.

              Discrimination between self and non-self by lectins (carbohydrate-binding proteins) is a strategy of innate immunity that is found in both vertebrates and invertebrates. In vertebrates, immune recognition mediated by ficolins (lectins that consist of a fibrinogen-like and a collagen-like domain), as well as by mannose-binding lectins, triggers the activation of the complement system, which results in the activation of novel serine proteases. The presence of a similar lectin-based complement system in ascidians, our closest invertebrate relatives, indicates that the complement system probably had a pivotal role in innate immunity before the evolution of an adaptive immune system in jawed vertebrates.
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                Author and article information

                Journal
                J Clin Biochem Nutr
                JCBN
                Journal of Clinical Biochemistry and Nutrition
                the Society for Free Radical Research Japan (Kyoto, Japan )
                0912-0009
                1880-5086
                November 2010
                20 October 2010
                : 47
                : 3
                : 217-223
                Affiliations
                [1 ]Department of Gastroenterology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan
                [2 ]Department of Gastroenterology, Kanazawa Medical University, 1-1 Daigaku, Uchinadamachi, Ishikawa 920-0293, Japan
                Author notes
                *To whom correspondence should be addressed. E-mail: tomomiccyu@ 123456yahoo.co.jp
                Article
                jcbn10-40
                10.3164/jcbn.10-40
                2966931
                21103030
                46e486b2-5e55-420d-bb64-003895b9a95d
                Copyright © 2010 JCBN

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 9 April 2010
                : 1 July 2010
                Categories
                Original Article

                Biochemistry
                h. pylori,polymorphism,mbl2,functional dyspepsia,tlr2
                Biochemistry
                h. pylori, polymorphism, mbl2, functional dyspepsia, tlr2

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