Abstract
The association of narcolepsy-cataplexy, a sleep disorder caused by the loss of hypocretin/orexin neurons in the hypothalamus, with DQA1*01:02-DQB1*06:02 is one of the tightest known single-allele human leukocyte antigen (HLA) associations. In this study, we explored genome-wide expression in peripheral white blood cells of 50 narcolepsy versus 47 controls (half of whom were DQB1*06:02 positive) and observed the largest differences between the groups in the signal from HLA probes. Further studies of HLA-DQ expression (mRNA and protein in a subset) in 125 controls and 147 narcolepsy cases did not reveal any difference, a result we explain by the lack of proper control of allelic diversity in Affymetrix HLA probes. Rather, a clear effect of DQB1*06:02 allelic dosage on DQB1*06:02 mRNA levels (1.65-fold) and protein (1.59-fold) could be demonstrated independent of disease status. These results indicate that allelic dosage is transmitted into changes in heterodimer availability, a phenomenon that may explain the increased risk for narcolepsy in DQB1*06:02 homozygotes versus heterozygotes.
| Original language | English |
|---|---|
| Journal | Human Immunology |
| Volume | 73 |
| Issue number | 4 |
| Pages (from-to) | 405-10 |
| Number of pages | 6 |
| ISSN | 0198-8859 |
| DOIs | |
| Publication status | Published - Apr 2012 |
Keywords
- Adult
- Alleles
- B-Lymphocytes/immunology
- Case-Control Studies
- Female
- Gene Dosage
- Gene Expression
- Gene Expression Profiling
- Genotype
- HLA-DQ beta-Chains/genetics
- Humans
- Male
- Narcolepsy/genetics
