Association of LY9 in UK and Canadian SLE families View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2008-03

AUTHORS

D S Cunninghame Graham, T J Vyse, P R Fortin, A Montpetit, Y-c Cai, S Lim, T McKenzie, L Farwell, B Rhodes, L Chad, T J Hudson, A Sharpe, C Terhorst, C M T Greenwood, J Wither, J D Rioux

ABSTRACT

Systemic lupus erythematosus (SLE) is a complex disease trait of unknown aetiology. Genome-wide linkage studies in human SLE identified several linkage regions, including one at 1q23, which contains multiple susceptibility genes, including the members of the signalling lymphocyte activation molecule (SLAM) locus. In mice there is a syntenic linkage region, Sle1. The SLAM genes are functionally related cell-surface receptors, which regulate signal transduction of cells in the immune system. Family-based association study in UK and Canadian SLE families identified variants in the promoter and coding region of SLAMF7 and LY9 contributing to SLE disease susceptibility. The strongest association was from rs509749, in exon 8 of LY9 (P=0.00209). rs509749 encodes a Val/Met nonsynonymous change in amino acid 602 in the cytoplasmic domain of LY9. In the parents and affected individuals from the Canadian SLE families, the risk allele of rs509049 skews the T-cell population by increasing the number of CD8+ memory T cells, while decreasing the proportion of CD4+ naïve T cells and activated T cells. Since rs509749 lies within the consensus binding site for SAP/SH2D1a, which influences downstream signalling events from LY9, the mechanism for increased CD8+ memory T cells may include differential binding SAP/SH2D1a to the cytoplasmic domain of LY9. More... »

PAGES

6364453

References to SciGraph publications

  • 2002-10-07. MALDI-TOF Mass Spectrometry-Based SNP Genotyping in SINGLE NUCLEOTIDE POLYMORPHISMS
  • 2003-01. The dual-function CD150 receptor subfamily: the viral attraction in NATURE IMMUNOLOGY
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/sj.gene.6364453

    DOI

    http://dx.doi.org/10.1038/sj.gene.6364453

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1049435440

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/18216865


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