The rs4774 CIITA missense variant is associated with risk of systemic lupus erythematosus
Open Access
- 26 May 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in Genes & Immunity
- Vol. 12 (8), 667-671
- https://doi.org/10.1038/gene.2011.36
Abstract
The major histocompatibility complex (MHC) class II transactivator gene (CIITA) encodes an important transcription factor required for human leukocyte antigens (HLA) class II MHC-restricted antigen presentation. MHC genes, including the HLA class II DRB1*03:01 allele, are strongly associated with systemic lupus erythematosus (SLE). Recently the rs4774 CIITA missense variant (+1632G/C) was reported to be associated with susceptibility to multiple sclerosis. In the current study, we investigated CIITA, DRB1*03:01 and risk of SLE using a multi-stage analysis. In stage 1, 9 CIITA variants were tested in 658 cases and 1363 controls (N=2021). In stage 2, rs4774 was tested in 684 cases and 2938 controls (N=3622). We also performed a meta-analysis of the pooled 1342 cases and 4301 controls (N=5643). In stage 1, rs4774*C was associated with SLE (odds ratio (OR)=1.24, 95% confidence interval (95% CI)=1.07–1.44, P=4.2 × 10−3). Similar results were observed in stage 2 (OR=1.16, 95% CI=1.02–1.33, P=8.5 × 10−3) and the meta-analysis of the combined data set (OR=1.20, 95% CI=1.09–1.33, Pmeta=2.5 × 10−4). In all three analyses, the strongest evidence for association between rs4774*C and SLE was present in individuals who carried at least one copy of DRB1*03:01 (Pmeta=1.9 × 10−3). Results support a role for CIITA in SLE, which appears to be stronger in the presence of DRB1*03:01.This publication has 43 references indexed in Scilit:
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