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- Title
The rs4774 CIITA missense variant is associated with risk of systemic lupus erythematosus.
- Authors
Bronson, P G; Goldstein, B A; Ramsay, P P; Beckman, K B; Noble, J A; Lane, J A; Seldin, M F; Kelly, J A; Harley, J B; Moser, K L; Gaffney, P M; Behrens, T W; Criswell, L A; Barcellos, L F
- 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.
- Subjects
SYSTEMIC lupus erythematosus; MAJOR histocompatibility complex; TRANSCRIPTION factors; HLA histocompatibility antigens; MULTIPLE sclerosis; META-analysis; GENE frequency; ANTIGEN presenting cells
- Publication
Genes & Immunity, 2011, Vol 12, Issue 8, p667
- ISSN
1466-4879
- Publication type
Article
- DOI
10.1038/gene.2011.36