title: The rs4774 CIITA missense variant is associated with risk of systemic lupus erythematosus.
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.
authors: Division of Epidemiology, Genetic Epidemiology and Genomics Laboratory, School of Public Health, University of California, Berkeley, CA 94720-7356, USA.
authors: P G
authors: PG
authors: Bronson
authors: B A
authors: BA
authors: Goldstein
authors: P P
authors: PP
authors: Ramsay
authors: K B
authors: KB
authors: Beckman
authors: J A
authors: JA
authors: Noble
authors: J A
authors: JA
authors: Lane
authors: M F
authors: MF
authors: Seldin
authors: J A
authors: JA
authors: Kelly
authors: J B
authors: JB
authors: Harley
authors: K L
authors: KL
authors: Moser
authors: P M
authors: PM
authors: Gaffney
authors: T W
authors: TW
authors: Behrens
authors: L A
authors: LA
authors: Criswell
authors: L F
authors: LF
authors: Barcellos
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