The rs4774 CIITA missense variant is associated with risk of systemic lupus erythematosus

P. G. Bronson; B. A. Goldstein; P. P. Ramsay; K. B. Beckman; J. A. Noble; J. A. Lane; Michael F Seldin; J. A. Kelly; J. B. Harley; K. L. Moser; P. M. Gaffney; T. W. Behrens; L. A. Criswell; L. F. Barcellos

doi:10.1038/gene.2011.36

The rs4774 CIITA missense variant is associated with risk of systemic lupus erythematosus

P. G. Bronson, B. A. Goldstein, P. P. Ramsay, K. B. Beckman, J. A. Noble, J. A. Lane, Michael F Seldin, J. A. Kelly, J. B. Harley, K. L. Moser, P. M. Gaffney, T. W. Behrens, L. A. Criswell, L. F. Barcellos

Biochemistry and Molecular Medicine

Research output: Contribution to journal › Article

18 Scopus citations

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)
Pages (from-to)	667-671
Number of pages	5
Journal	Genes and Immunity
Volume	12
Issue number	8
DOIs	https://doi.org/10.1038/gene.2011.36
State	Published - Dec 2011

Keywords

autoimmunity
CIITA
HLA
major histocompatibility complex
MHC2TA
systemic lupus erythematosus

ASJC Scopus subject areas

Genetics(clinical)
Immunology
Genetics

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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. (2011). The rs4774 CIITA missense variant is associated with risk of systemic lupus erythematosus. Genes and Immunity, 12(8), 667-671. https://doi.org/10.1038/gene.2011.36

The rs4774 CIITA missense variant is associated with risk of systemic lupus erythematosus. / Bronson, P. G.; Goldstein, B. A.; Ramsay, P. P.; Beckman, K. B.; Noble, J. A.; Lane, J. A.; Seldin, Michael F; Kelly, J. A.; Harley, J. B.; Moser, K. L.; Gaffney, P. M.; Behrens, T. W.; Criswell, L. A.; Barcellos, L. F.

In: Genes and Immunity, Vol. 12, No. 8, 12.2011, p. 667-671.

Research output: Contribution to journal › Article

Bronson, P. G. ; Goldstein, B. A. ; Ramsay, P. P. ; Beckman, K. B. ; Noble, J. A. ; Lane, J. A. ; Seldin, Michael F ; Kelly, J. A. ; Harley, J. B. ; Moser, K. L. ; Gaffney, P. M. ; Behrens, T. W. ; Criswell, L. A. ; Barcellos, L. F. / The rs4774 CIITA missense variant is associated with risk of systemic lupus erythematosus. In: Genes and Immunity. 2011 ; Vol. 12, No. 8. pp. 667-671.

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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.",

keywords = "autoimmunity, CIITA, HLA, major histocompatibility complex, MHC2TA, systemic lupus erythematosus",

author = "Bronson, {P. G.} and Goldstein, {B. A.} and Ramsay, {P. P.} and Beckman, {K. B.} and Noble, {J. A.} and Lane, {J. A.} and Seldin, {Michael F} and Kelly, {J. A.} and Harley, {J. B.} and Moser, {K. L.} and Gaffney, {P. M.} and Behrens, {T. W.} and Criswell, {L. A.} and Barcellos, {L. F.}",

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AU - Goldstein, B. A.

AU - Ramsay, P. P.

AU - Beckman, K. B.

AU - Noble, J. A.

AU - Lane, J. A.

AU - Seldin, Michael F

AU - Kelly, J. A.

AU - Harley, J. B.

AU - Moser, K. L.

AU - Gaffney, P. M.

AU - Behrens, T. W.

AU - Criswell, L. A.

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