PMID- 22586495
OWN - NLM
STAT- MEDLINE
DCOM- 20120926
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 5
DP  - 2012
TI  - Importance of human leukocyte antigen (HLA) class I and II alleles on the risk of 
      multiple sclerosis.
PG  - e36779
LID - 10.1371/journal.pone.0036779 [doi]
LID - e36779
AB  - Multiple sclerosis (MS) is a complex disease of the central nervous system of 
      unknown etiology. The human leukocyte antigen (HLA) locus on chromosome 6 confers 
      a considerable part of the susceptibility to MS, and the most important factor is 
      the class II allele HLA-DRB1*15:01. In addition, we and others have previously 
      established a protective effect of HLA-A*02. Here, we genotyped 1,784 patients 
      and 1,660 healthy controls from Scandinavia for the HLA-A, HLA-B, HLA-C and 
      HLA-DRB1 genes and investigated their effects on MS risk by logistic regression. 
      Several allele groups were found to exert effects independently of DRB1*15 and 
      A*02, in particular DRB1*01 (OR = 0.82, p = 0.034) and B*12 (including B*44/45, 
      OR = 0.76, p = 0.0028), confirming previous reports. Furthermore, we observed 
      interaction between allele groups: DRB1*15 and DRB1*01 (multiplicative: OR = 
      0.54, p = 0.0041; additive: AP = 0.47, p = 4 x 10(-06)), DRB1*15 and C*12 
      (multiplicative: OR = 0.37, p = 0.00035; additive: AP = 0.58, p = 2.6 x 10(-05)), 
      indicating that the effect size of these allele groups varies when taking DRB1*15 
      into account. Analysis of inferred haplotypes showed that almost all DRB1*15 
      bearing haplotypes were risk haplotypes, and that all A*02 bearing haplotypes 
      were protective as long as they did not carry DRB1*15. In contrast, we found one 
      class I haplotype, carrying A*02-C*05-B*12, which abolished the risk of DRB1*15. 
      In conclusion, these results confirms a complex role of HLA class I and II genes 
      that goes beyond DRB1*15 and A*02, in particular by including all three classical 
      HLA class I genes as well as functional interactions between DRB1*15 and several 
      alleles of DRB1 and class I genes.
FAU - Link, Jenny
AU  - Link J
AD  - Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. 
      jenny.link@ki.se
FAU - Kockum, Ingrid
AU  - Kockum I
FAU - Lorentzen, Aslaug R
AU  - Lorentzen AR
FAU - Lie, Benedicte A
AU  - Lie BA
FAU - Celius, Elisabeth G
AU  - Celius EG
FAU - Westerlind, Helga
AU  - Westerlind H
FAU - Schaffer, Marie
AU  - Schaffer M
FAU - Alfredsson, Lars
AU  - Alfredsson L
FAU - Olsson, Tomas
AU  - Olsson T
FAU - Brynedal, Boel
AU  - Brynedal B
FAU - Harbo, Hanne F
AU  - Harbo HF
FAU - Hillert, Jan
AU  - Hillert J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120507
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-DRB1 Chains)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Alleles
MH  - Female
MH  - Genetic Association Studies
MH  - Genetic Predisposition to Disease
MH  - *HLA-A Antigens/genetics
MH  - *HLA-B Antigens/genetics
MH  - HLA-DRB1 Chains/*genetics
MH  - Haplotypes
MH  - Humans
MH  - Linkage Disequilibrium
MH  - Male
MH  - Middle Aged
MH  - Multiple Sclerosis/*genetics
MH  - Polymorphism, Single Nucleotide
MH  - Scandinavian and Nordic Countries
PMC - PMC3346735
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/05/16 06:00
MHDA- 2012/09/27 06:00
PMCR- 2012/05/07
CRDT- 2012/05/16 06:00
PHST- 2011/08/01 00:00 [received]
PHST- 2012/04/06 00:00 [accepted]
PHST- 2012/05/16 06:00 [entrez]
PHST- 2012/05/16 06:00 [pubmed]
PHST- 2012/09/27 06:00 [medline]
PHST- 2012/05/07 00:00 [pmc-release]
AID - PONE-D-11-15207 [pii]
AID - 10.1371/journal.pone.0036779 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(5):e36779. doi: 10.1371/journal.pone.0036779. Epub 2012 May 7.