Genetic association of CD247 (CD3ζ) with SLE in a large-scale multiethnic study

A classic T-cell phenotype in Systemic lupus erythematosus (SLE) is the downregulation and replacement of the CD3ζ chain that alters TCR signaling. However, genetic associations with SLE in the human CD247 locus that encodes CD3ζ are not well established and require replication in independent cohorts. Our aim was therefore to examine, localize and validate CD247-SLE association in a large multi-ethnic population. We typed 44 contiguous CD247 SNPs in 8 922 SLE patients and 8 077 controls from four ethnically distinct populations. The strongest associations were found in the Asian population (11 SNPs in intron 1, 4.99×10−4Phap=2.12×10−5) that exceeded the most associated single SNP rs858554 (MAFControls=13%; P=4.99×10−4, OR=1.32) in significance. Imputation and subsequent association analysis showed evidence of association (P<0.05) at 27 additional SNPs within intron 1. Cross-ethnic meta-analysis, assuming an additive genetic model adjusted for population proportions, showed 5 SNPs with significant P-values (1.40×10−3Bonferroni correction (Pmeta=2.66×10−2). Our study independently confirms and extends the association of SLE with CD247, which is shared by various autoimmune disorders and supports a common T cell-mediated mechanism.