Association of LY9 in UK and Canadian SLE families
Autor: | Timothy J. Vyse, Thomas J. Hudson, Benjamin Rhodes, Joan E. Wither, S. Lim, CaNIOS GenES Investigators, Arlene H. Sharpe, Tamara McKenzie, Lauren Chad, John D. Rioux, Celia M. T. Greenwood, Alexandre Montpetit, L. Farwell, Y-C Cai, D S Cunninghame Graham, Cox Terhorst, Paul R. Fortin |
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Rok vydání: | 2008 |
Předmět: |
Nonsynonymous substitution
Canada Genetic Linkage Immunology Population Locus (genetics) Biology Polymorphism Single Nucleotide Antigen Antigens CD Signaling Lymphocytic Activation Molecule Family Genetic linkage Genetics medicine Humans Lupus Erythematosus Systemic Genetic Predisposition to Disease Allele education Alleles Genetics (clinical) education.field_of_study Membrane Glycoproteins Lupus erythematosus medicine.disease United Kingdom Pedigree CD8 |
Zdroj: | Genes & Immunity. 9:93-102 |
ISSN: | 1476-5470 1466-4879 |
Popis: | 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. |
Databáze: | OpenAIRE |
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