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, P meta=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 (P meta=1.9×10 -3). Results support a role for CIITA in SLE, which appears to be stronger in the presence of DRB1*03:01.
Original language | English (US) |
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Pages (from-to) | 667-671 |
Number of pages | 5 |
Journal | Genes and Immunity |
Volume | 12 |
Issue number | 8 |
DOIs | |
State | Published - Dec 2011 |
Keywords
- autoimmunity
- CIITA
- HLA
- major histocompatibility complex
- MHC2TA
- systemic lupus erythematosus
ASJC Scopus subject areas
- Genetics(clinical)
- Immunology
- Genetics