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  • Gyllenberg, AKarolinska Institutet (author)

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

  • Article/chapterEnglish2014

Publisher, publication year, extent ...

  • 2014-01-16
  • Stockholm :Springer Science and Business Media LLC,2014

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/194001
  • ISSN:1466-4879
  • 10616/44520hdl
  • https://gup.ub.gu.se/publication/194001URI
  • https://doi.org/10.1038/gene.2013.71DOI
  • https://lup.lub.lu.se/record/4291325URI
  • http://hdl.handle.net/10616/44520URI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:128743988URI

Supplementary language notes

  • Language:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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.

Subject headings and genre

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  • Piehl, FKarolinska Institutet (author)
  • Alfredsson, LKarolinska Institutet (author)
  • Hillert, JKarolinska Institutet (author)
  • Bomfim, I LKarolinska Institutet (author)
  • Padyukov, LKarolinska Institutet (author)
  • Orho-Melander, MarjuLund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups(Swepub:lu)endo-mor (author)
  • Lindholm, EeroLund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Department of Clinical Sciences, Malmö,Faculty of Medicine(Swepub:lu)endo-eli (author)
  • Landin-Olsson, MonaLund University,Lunds universitet,Medicin, Lund,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Medicine, Lund,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)med-mla (author)
  • Lernmark, ÅkeLund University,Lunds universitet,Celiaki och diabetes,Forskargrupper vid Lunds universitet,Celiac Disease and Diabetes Unit,Lund University Research Groups(Swepub:lu)endo-ale (author)
  • Aili, M (author)
  • Bååth, L E (author)
  • Carlsson, E (author)
  • Edenwall, H (author)
  • Forsander, Gun,1951Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för pediatrik,Institute of Clinical Sciences, Department of Pediatrics(Swepub:gu)xfgunj (author)
  • Granström, B W (author)
  • Gustavsson, I (author)
  • Hanas, R (author)
  • Hellenberg, L (author)
  • Hellgren, H (author)
  • Holmberg, E (author)
  • Hörnell, H (author)
  • Ivarsson, Sten-A (author)
  • Johansson, C (author)
  • Jonsell, G (author)
  • Kockum, KKarolinska Institutet (author)
  • Lindblad, B (author)
  • Lindh, A (author)
  • Ludvigsson, J (author)
  • Myrdal, U (author)
  • Neiderud, J (author)
  • Segnestam, K (author)
  • Sjö, S (author)
  • Skogsberg, L (author)
  • Strömberg, L (author)
  • Ståhle, U (author)
  • Thalme, B (author)
  • Tullus, K (author)
  • Tuvemo, TKarolinska Institutet (author)
  • Wallensteen, M (author)
  • Westphal, O (author)
  • Aman, J (author)
  • Arnqvist, H (author)
  • Björck, E (author)
  • Eriksson, J (author)
  • Nyström, L (author)
  • Ohlson, L O (author)
  • Scherstén, B (author)
  • Ostman, J (author)
  • Olsson, T (author)
  • Kockum, I (author)
  • Karolinska InstitutetDiabetes - kardiovaskulär sjukdom (creator_code:org_t)
  • Karolinska Institutet
  • Karolinska Institutet

Related titles

  • In:Genes and immunityStockholm : Springer Science and Business Media LLC15, s. 162-1671476-54701466-4879

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