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

Research output: Contribution to journalArticle

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.

Details

Authors
  • A Gyllenberg
  • F Piehl
  • L Alfredsson
  • J Hillert
  • I L Bomfim
  • L Padyukov
  • 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
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes
Original languageEnglish
Pages (from-to)162-167
JournalGenes and Immunity
Volume15
Issue number3
Publication statusPublished - 2014
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Diabetes and cardiovascular disease - genetic epidemiology (013241590), Diabetes and Celiac Unit (013241540), Pediatrics/Urology/Gynecology/Endocrinology (013240400), Medicine (Lund) (013230025)