PMID- 24430172
OWN - NLM
STAT- MEDLINE
DCOM- 20141205
LR  - 20211021
IS  - 1476-5470 (Electronic)
IS  - 1466-4879 (Linking)
VI  - 15
IP  - 3
DP  - 2014 Apr-May
TI  - Variability in the CIITA gene interacts with HLA in multiple sclerosis.
PG  - 162-7
LID - 10.1038/gene.2013.71 [doi]
AB  - 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.
FAU - Gyllenberg, A
AU  - Gyllenberg A
AD  - Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institutet, 
      Stockholm, Sweden.
FAU - Piehl, F
AU  - Piehl F
AD  - Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institutet, 
      Stockholm, Sweden.
FAU - Alfredsson, L
AU  - Alfredsson L
AD  - Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
FAU - Hillert, J
AU  - Hillert J
AD  - Department of Clinical Neuroscience, Multiple Sclerosis Research Group, 
      Karolinska Institutet, Stockholm, Sweden.
FAU - Bomfim, I L
AU  - Bomfim IL
AD  - Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institutet, 
      Stockholm, Sweden.
FAU - Padyukov, L
AU  - Padyukov L
AD  - Department of Medicine, Rheumatology Unit, Karolinska Institutet, Stockholm, 
      Sweden.
FAU - Orho-Melander, M
AU  - Orho-Melander M
AD  - Department of Clinical Sciences, Diabetes and Cardiovascular Disease, Genetic 
      Epidemiology, Lund University Hospital, Lund, Sweden.
FAU - Lindholm, E
AU  - Lindholm E
AD  - Department of Clinical Sciences, Diabetes and Cardiovascular Disease, Genetic 
      Epidemiology, Lund University Hospital, Lund, Sweden.
FAU - Landin-Olsson, M
AU  - Landin-Olsson M
AD  - Department of Endocrinology, Skane University Hospital Lund, Lund University, 
      Lund, Sweden.
FAU - Lernmark, A
AU  - Lernmark A
AD  - Department of Medicine, Lund University Hospital, Lund, Sweden.
CN  - Swedish Childhood Diabetes Study Group
CN  - Diabetes Incidence in Sweden Study Group
FAU - Olsson, T
AU  - Olsson T
AD  - Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institutet, 
      Stockholm, Sweden.
FAU - Kockum, I
AU  - Kockum I
AD  - Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institutet, 
      Stockholm, Sweden.
LA  - eng
PT  - Journal Article
DEP - 20140116
PL  - England
TA  - Genes Immun
JT  - Genes and immunity
JID - 100953417
RN  - 0 (HLA Antigens)
RN  - 0 (MHC class II transactivator protein)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Trans-Activators)
SB  - IM
MH  - Alleles
MH  - Case-Control Studies
MH  - *Epistasis, Genetic
MH  - Gene Frequency
MH  - *Genetic Variation
MH  - Genotype
MH  - HLA Antigens/*genetics/immunology
MH  - Humans
MH  - Linkage Disequilibrium
MH  - Multiple Sclerosis/epidemiology/*genetics/immunology
MH  - Nuclear Proteins/*genetics
MH  - Odds Ratio
MH  - Polymorphism, Single Nucleotide
MH  - Trans-Activators/*genetics
FIR - Aili, M
IR  - Aili M
FIR - Baath, L E
IR  - Baath LE
FIR - Carlsson, E
IR  - Carlsson E
FIR - Edenwall, H
IR  - Edenwall H
FIR - Forsander, G
IR  - Forsander G
FIR - Granstrom, B W
IR  - Granstrom BW
FIR - Gustavsson, I
IR  - Gustavsson I
FIR - Hanas, R
IR  - Hanas R
FIR - Hellenberg, L
IR  - Hellenberg L
FIR - Hellgren, H
IR  - Hellgren H
FIR - Holmberg, E
IR  - Holmberg E
FIR - Hornell, H
IR  - Hornell H
FIR - Ivarsson, Sten-A
IR  - Ivarsson SA
FIR - Johansson, C
IR  - Johansson C
FIR - Jonsell, G
IR  - Jonsell G
FIR - Kockum, K
IR  - Kockum K
FIR - Lindblad, B
IR  - Lindblad B
FIR - Lindh, A
IR  - Lindh A
FIR - Ludvigsson, J
IR  - Ludvigsson J
FIR - Myrdal, U
IR  - Myrdal U
FIR - Neiderud, J
IR  - Neiderud J
FIR - Segnestam, K
IR  - Segnestam K
FIR - Sjo, S
IR  - Sjo S
FIR - Skogsberg, L
IR  - Skogsberg L
FIR - Stromberg, L
IR  - Stromberg L
FIR - Stahle, U
IR  - Stahle U
FIR - Thalme, B
IR  - Thalme B
FIR - Tullus, K
IR  - Tullus K
FIR - Tuvemo, T
IR  - Tuvemo T
FIR - Wallensteen, M
IR  - Wallensteen M
FIR - Westphal, O
IR  - Westphal O
FIR - Aman, J
IR  - Aman J
FIR - Arnqvist, H
IR  - Arnqvist H
FIR - Bjorck, E
IR  - Bjorck E
FIR - Eriksson, J
IR  - Eriksson J
FIR - Nystrom, L
IR  - Nystrom L
FIR - Ohlson, L O
IR  - Ohlson LO
FIR - Schersten, B
IR  - Schersten B
FIR - Ostman, J
IR  - Ostman J
EDAT- 2014/01/17 06:00
MHDA- 2014/12/15 06:00
CRDT- 2014/01/17 06:00
PHST- 2013/08/20 00:00 [received]
PHST- 2013/11/12 00:00 [revised]
PHST- 2013/12/03 00:00 [accepted]
PHST- 2014/01/17 06:00 [entrez]
PHST- 2014/01/17 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
AID - gene201371 [pii]
AID - 10.1038/gene.2013.71 [doi]
PST - ppublish
SO  - Genes Immun. 2014 Apr-May;15(3):162-7. doi: 10.1038/gene.2013.71. Epub 2014 Jan 
      16.