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

Author:
  • A Gyllenberg
  • F Piehl
  • L Alfredsson
  • J Hillert
  • I L Bomfim
  • L Padyukov
  • Marju Orho-Melander
  • Eero Lindholm
  • Mona Landin-Olsson
  • Åke Lernmark
  • M Aili
  • L E Bååth
  • E Carlsson
  • H Edenwall
  • G Forsander
  • B W Granström
  • I Gustavsson
  • R Hanas
  • L Hellenberg
  • H Hellgren
  • E Holmberg
  • H Hörnell
  • Sten-A Ivarsson
  • C Johansson
  • G Jonsell
  • K Kockum
  • B Lindblad
  • A Lindh
  • J Ludvigsson
  • U Myrdal
  • Jan Neiderud
  • K Segnestam
  • S Sjö
  • L Skogsberg
  • L Strömberg
  • U Ståhle
  • B Thalme
  • K Tullus
  • T Tuvemo
  • M Wallensteen
  • O Westphal
  • J Aman
  • H Arnqvist
  • E Björck
  • J Eriksson
  • L Nyström
  • L O Ohlson
  • B Scherstén
  • J Ostman
  • T Olsson
  • I Kockum
Publishing year: 2014
Language: English
Pages: 162-167
Publication/Series: Genes and Immunity
Volume: 15
Issue: 3
Document type: Journal article
Publisher: Nature Publishing Group

Abstract english

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.

Keywords

  • Endocrinology and Diabetes

Other

Published
  • Diabetes - Cardiovascular Disease
  • Diabetes and Celiac Unit
  • ISSN: 1476-5470
E-mail: ake [dot] lernmark [at] med [dot] lu [dot] se

Principal investigator

Diabetes and Celiac Unit

+46 40 39 19 01

+46 70 616 47 79

60:11:015

Jan Waldenströms gata 35, Malmö

33

Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00