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Variability in the CIITA gene interacts with HLA in multiple sclerosis.

Gyllenberg, A; Piehl, F; Alfredsson, L; Hillert, J; Bomfim, I L; Padyukov, L; Orho-Melander, Marju LU ; Lindholm, Eero LU ; Landin-Olsson, Mona LU and Lernmark, Åke LU , et al. (2014) In Genes and Immunity 15(3). p.162-167
Abstract
The human leukocyte antigen (HLA) is the main genetic determinant of multiple sclerosis (MS) risk. Within the HLA, the class II HLA-DRB1*15:01 allele exerts a disease-promoting effect, whereas the class I HLA-A*02 allele is protective. The CIITA gene is crucial for expression of class II HLA molecules and has previously been found to associate with several autoimmune diseases, including MS and type 1 diabetes. We here performed association analyses with CIITA in 2000 MS cases and up to 6900 controls as well as interaction analysis with HLA. We find that the previously investigated single-nucleotide polymorphism rs4774 is associated with MS risk in cases carrying the HLA-DRB1*15 allele (P=0.01, odds ratio (OR): 1.21, 95% confidence interval... (More)
The human leukocyte antigen (HLA) is the main genetic determinant of multiple sclerosis (MS) risk. Within the HLA, the class II HLA-DRB1*15:01 allele exerts a disease-promoting effect, whereas the class I HLA-A*02 allele is protective. The CIITA gene is crucial for expression of class II HLA molecules and has previously been found to associate with several autoimmune diseases, including MS and type 1 diabetes. We here performed association analyses with CIITA in 2000 MS cases and up to 6900 controls as well as interaction analysis with HLA. We find that the previously investigated single-nucleotide polymorphism rs4774 is associated with MS risk in cases carrying the HLA-DRB1*15 allele (P=0.01, odds ratio (OR): 1.21, 95% confidence interval (CI): 1.04-1.40) or the HLA-A*02 allele (P=0.01, OR: 1.33, 95% CI: 1.07-1.64) and that these associations are independent of the adjacent confirmed MS susceptibility gene CLEC16A. We also confirm interaction between rs4774 and HLA-DRB1*15:01 such that individuals carrying the risk allele for rs4774 and HLA-DRB1*15:01 have a higher than expected risk for MS. In conclusion, our findings support previous data that variability in the CIITA gene affects MS risk, but also that the effect is modulated by MS-associated HLA haplotypes. These findings further underscore the biological importance of HLA for MS risk.Genes and Immunity advance online publication, 16 January 2014; doi:10.1038/gene.2013.71. (Less)
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Genes and Immunity
volume
15
issue
3
pages
162 - 167
publisher
Nature Publishing Group
external identifiers
  • pmid:24430172
  • wos:000334981400004
  • scopus:84899586524
ISSN
1476-5470
DOI
10.1038/gene.2013.71
language
English
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yes
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de864922-2398-461e-b24e-0452c0959fc5 (old id 4291325)
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http://www.ncbi.nlm.nih.gov/pubmed/24430172?dopt=Abstract
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2014-02-07 23:31:40
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2017-07-23 03:23:47
@article{de864922-2398-461e-b24e-0452c0959fc5,
  abstract     = {The human leukocyte antigen (HLA) is the main genetic determinant of multiple sclerosis (MS) risk. Within the HLA, the class II HLA-DRB1*15:01 allele exerts a disease-promoting effect, whereas the class I HLA-A*02 allele is protective. The CIITA gene is crucial for expression of class II HLA molecules and has previously been found to associate with several autoimmune diseases, including MS and type 1 diabetes. We here performed association analyses with CIITA in 2000 MS cases and up to 6900 controls as well as interaction analysis with HLA. We find that the previously investigated single-nucleotide polymorphism rs4774 is associated with MS risk in cases carrying the HLA-DRB1*15 allele (P=0.01, odds ratio (OR): 1.21, 95% confidence interval (CI): 1.04-1.40) or the HLA-A*02 allele (P=0.01, OR: 1.33, 95% CI: 1.07-1.64) and that these associations are independent of the adjacent confirmed MS susceptibility gene CLEC16A. We also confirm interaction between rs4774 and HLA-DRB1*15:01 such that individuals carrying the risk allele for rs4774 and HLA-DRB1*15:01 have a higher than expected risk for MS. In conclusion, our findings support previous data that variability in the CIITA gene affects MS risk, but also that the effect is modulated by MS-associated HLA haplotypes. These findings further underscore the biological importance of HLA for MS risk.Genes and Immunity advance online publication, 16 January 2014; doi:10.1038/gene.2013.71.},
  author       = {Gyllenberg, A and Piehl, F and Alfredsson, L and Hillert, J and Bomfim, I L and Padyukov, L and Orho-Melander, Marju and Lindholm, Eero and Landin-Olsson, Mona and Lernmark, Åke and Aili, M and Bååth, L E and Carlsson, E and Edenwall, H and Forsander, G and Granström, B W and Gustavsson, I and Hanas, R and Hellenberg, L and Hellgren, H and Holmberg, E and Hörnell, H and Ivarsson, Sten-A and Johansson, C and Jonsell, G and Kockum, K and Lindblad, B and Lindh, A and Ludvigsson, J and Myrdal, U and Neiderud, Jan and Segnestam, K and Sjö, S and Skogsberg, L and Strömberg, L and Ståhle, U and Thalme, B and Tullus, K and Tuvemo, T and Wallensteen, M and Westphal, O and Aman, J and Arnqvist, H and Björck, E and Eriksson, J and Nyström, L and Ohlson, L O and Scherstén, B and Ostman, J and Olsson, T and Kockum, I},
  issn         = {1476-5470},
  language     = {eng},
  number       = {3},
  pages        = {162--167},
  publisher    = {Nature Publishing Group},
  series       = {Genes and Immunity},
  title        = {Variability in the CIITA gene interacts with HLA in multiple sclerosis.},
  url          = {http://dx.doi.org/10.1038/gene.2013.71},
  volume       = {15},
  year         = {2014},
}