PMID- 25277311
OWN - NLM
STAT- MEDLINE
DCOM- 20150311
LR  - 20211021
IS  - 1432-1211 (Electronic)
IS  - 0093-7711 (Linking)
VI  - 67
IP  - 1
DP  - 2015 Jan
TI  - HLA dosage effect in narcolepsy with cataplexy.
PG  - 1-6
LID - 10.1007/s00251-014-0808-z [doi]
AB  - Narcolepsy with cataplexy is a sleep disorder caused by the loss of 
      hypocretin-producing neurons in the hypothalamus. It is tightly associated with a 
      specific human leukocyte antigen (HLA)-allele: HLA-DQB1*06:02. Based on this, an 
      autoimmune process has been hypothesized. A functional HLA-DQ molecule consists 
      of a DQalpha and a DQbeta chain. HLA-DQB1*06:02 (DQbeta) has a strong preference for 
      binding to HLA-DQA1*01:02 (DQalpha), and together they form the functional DQ0602 
      dimer. A dosage effect would be expected if the HLA-DQ0602 dimer itself is 
      directly involved in the aetiology. An increased expression of the HLA-DQ0602 
      dimer is expected in individuals homozygous for HLA-DQB1*06:02-DQA1*01:02, but is 
      also hypothesized in individuals heterozygous for HLA-DQB1*06:02 and homozygous 
      for HLA-DQA1*01:02. To study the impact of the expression of the HLA-DQ0602 dimer 
      on narcolepsy susceptibility, 248 Dutch narcolepsy patients and 1272 Dutch 
      control subjects, all of them positive for DQB1*06:02 (heterozygous and 
      homozygous), were HLA-genotyped with attention not only to DQB1 but also to 
      DQA1*01:02. DQB1*06:02-DQA1*01:02 homozygosity was significantly more often seen 
      in patients compared to controls (O.R. 2.29) confirming previous observations. 
      More importantly, a significantly higher prevalence of homozygosity for 
      DQA1*01:02 was found in HLA-DQB1*06:02 heterozygous patients compared to controls 
      (O.R. 2.37, p < 0.001). The latter finding clearly supports a direct role of the 
      HLA-DQ molecule in the development of disease.
FAU - van der Heide, Astrid
AU  - van der Heide A
AD  - Department of Neurology and Clinical Neurophysiology, Leiden University Medical 
      Center, PO Box 9600, 2300, Leiden, The Netherlands, a.van_der_heide@lumc.nl.
FAU - Verduijn, Willem
AU  - Verduijn W
FAU - Haasnoot, Geert W
AU  - Haasnoot GW
FAU - Drabbels, Jos J M
AU  - Drabbels JJ
FAU - Lammers, Gert J
AU  - Lammers GJ
FAU - Claas, Frans H J
AU  - Claas FH
LA  - eng
PT  - Journal Article
DEP - 20141003
PL  - United States
TA  - Immunogenetics
JT  - Immunogenetics
JID - 0420404
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQB1 antigen)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Neuropeptides)
RN  - 0 (Orexins)
SB  - IM
MH  - Alleles
MH  - Autoimmune Diseases/*genetics/immunology
MH  - Genetic Predisposition to Disease
MH  - HLA-DQ beta-Chains/chemistry/*genetics/immunology
MH  - Heterozygote
MH  - Histocompatibility Testing
MH  - Homozygote
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/immunology/metabolism
MH  - Narcolepsy/etiology/genetics/*immunology
MH  - Neurons/*immunology/metabolism
MH  - Neuropeptides/immunology/metabolism
MH  - Orexins
EDAT- 2014/10/04 06:00
MHDA- 2015/03/12 06:00
CRDT- 2014/10/04 06:00
PHST- 2014/07/03 00:00 [received]
PHST- 2014/09/21 00:00 [accepted]
PHST- 2014/10/04 06:00 [entrez]
PHST- 2014/10/04 06:00 [pubmed]
PHST- 2015/03/12 06:00 [medline]
AID - 10.1007/s00251-014-0808-z [doi]
PST - ppublish
SO  - Immunogenetics. 2015 Jan;67(1):1-6. doi: 10.1007/s00251-014-0808-z. Epub 2014 Oct 
      3.