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Amanda J. Phipps-Green, Ruth K. G. Topless, Marilyn E. Merriman, Nicola Dalbeth, Peter J. Gow, Andrew A. Harrison, John Highton, Peter B. B. Jones, Lisa K. Stamp, Pille Harrison, Bryan P. Wordsworth, Tony R. Merriman, No evidence for association of the systemic lupus erythematosus-associated ITGAM variant, R77H, with rheumatoid arthritis in the Caucasian population, Rheumatology, Volume 48, Issue 12, December 2009, Pages 1614–1615, https://doi.org/10.1093/rheumatology/kep254
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Sir, A non-synonymous integrin-α-M (ITGAM) variant (R77H) confers a strong risk for SLE in Caucasian, African and Hispanic populations [odds ratio (OR)meta = 1.83] [1, 2]. ITGAM encodes the α-chain subunit of integrin-αMβ2, a cell surface receptor expressed predominantly on monocytes and neutrophils, which mediates activation, adhesion and migration of leucocytes through the endothelium, as well as phagocytosis of complement-coated particles, and neutrophil apoptosis [3]. Interaction of integrin-αMβ2 with intercellular adhesion molecules (ICAMs) mobilizes leucocytes to sites of inflammation, and in silico modelling suggests that the R77H substitution may alter the α1 domain that binds ICAM-1 [1, 3]. Polymorphism of ICAM-1 is implicated in susceptibility to RA: a K469E variant (rs5498) in ICAM-1 is associated with RA in Korean [4] and UK sample sets [5], but not in an Italian sample set [6].
SLE and RA are systemic autoimmune diseases that are known to share common genetic susceptibility through the 620W variant of PTPN22 [7], rs75674865 within STAT4 and several variants within TNFAIP3 [8]. We therefore tested for association of ITGAM R77H (rs1143679) with susceptibility to RA in Caucasian sample sets drawn from New Zealand (NZ) and the UK, including the Wellcome Trust Case Control Consortium (WTCCC).
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