Identification of MAMDC1 as a candidate susceptibility gene for systemic lupus erythematosus SLE.Reportar como inadecuado

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Reference: Hellquist, A, Zucchelli, M, Lindgren, CM et al., (2009). Identification of MAMDC1 as a candidate susceptibility gene for systemic lupus erythematosus (SLE). PloS one, 4 (12), Article: e8037.Citable link to this page:


Identification of MAMDC1 as a candidate susceptibility gene for systemic lupus erythematosus (SLE).

Abstract: BACKGROUND: Systemic lupus erythematosus (SLE) is a complex autoimmune disorder with multiple susceptibility genes. We have previously reported suggestive linkage to the chromosomal region 14q21-q23 in Finnish SLE families. PRINCIPAL FINDINGS: Genetic fine mapping of this region in the same family material, together with a large collection of parent affected trios from UK and two independent case-control cohorts from Finland and Sweden, indicated that a novel uncharacterized gene, MAMDC1 (MAM domain containing glycosylphosphatidylinositol anchor 2, also known as MDGA2, MIM 611128), represents a putative susceptibility gene for SLE. In a combined analysis of the whole dataset, significant evidence of association was detected for the MAMDC1 intronic single nucleotide polymorphisms (SNP) rs961616 (P -value = 0.001, Odds Ratio (OR) = 1.292, 95% CI 1.103-1.513) and rs2297926 (P -value = 0.003, OR = 1.349, 95% CI 1.109-1.640). By Northern blot, real-time PCR (qRT-PCR) and immunohistochemical (IHC) analyses, we show that MAMDC1 is expressed in several tissues and cell types, and that the corresponding mRNA is up-regulated by the pro-inflammatory cytokines tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) in THP-1 monocytes. Based on its homology to known proteins with similar structure, MAMDC1 appears to be a novel member of the adhesion molecules of the immunoglobulin superfamily (IgCAM), which is involved in cell adhesion, migration, and recruitment to inflammatory sites. Remarkably, some IgCAMs have been shown to interact with ITGAM, the product of another SLE susceptibility gene recently discovered in two independent genome wide association (GWA) scans. SIGNIFICANCE: Further studies focused on MAMDC1 and other molecules involved in these pathways might thus provide new insight into the pathogenesis of SLE.

Peer Review status:Peer reviewedPublication status:PublishedVersion:Publisher's version Funder: Academy of Finland   Funder: Sigrid Juselius Foundation and Finska Lakarsallskapet   Funder: Swedish Research Council   Funder: Finland Research Council   Funder: Helsinki University Central Hospital Research Fund   Funder: Welander-Finsen Foundation   Funder: Helsinki Biomedical Graduate School LERU PhD Program in Biomedicine   Funder: University of Helsinki Research Foundation   Funder: Biomedicum Helsinki Foundation   Funder: Swedish Heart-Lung Foundation   Funder: The Royal Physiographic Society in Lund   Funder: The King Gustaf V 80th Birthday Fund   Funder: The Ake Wiberg Foundation   Funder: Stockholm County Council   Notes:Copyright 2009 Hellquist et al. 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 author and source are credited.

Bibliographic Details

Publisher: Public Library of Science

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Journal: PloS onesee more from them

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Issue Date: 2009

pages:Article: e8037Identifiers

Urn: uuid:cbd15015-1614-471e-af9a-5df2cfcd151b

Source identifier: 7820

Eissn: 1932-6203


Issn: 1932-6203 Item Description

Type: Journal article;

Language: eng

Version: Publisher's versionKeywords: Humans Monocytes Cell Line Chromosomes, Human, Pair 14 Odds Ratio Phylogeny Sequence Homology, Amino Acid Gene Expression Regulation Genetic Loci Lupus Erythematosus, Systemic Cytokines Neural Cell Adhesion Molecules Genetic Linkage Genetic Predisposition to Disease GPI-Linked Proteins Polymorphism, Single Nucleotide RNA, Messenger Tiny URL: pubs:7820


Autor: Hellquist, A - - - Zucchelli, M - - - Lindgren, CM - institutionUniversity of Oxford Oxford, MSD, Clinical Medicine, WTC Human Ge



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