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Hum Immunol. 2012 Apr;73(4):405-10. doi: 10.1016/j.humimm.2012.01.004. Epub 2012 Jan 31.

DQB1*06:02 allele-specific expression varies by allelic dosage, not narcolepsy status.

Author information

1
Center for Sleep Sciences, Stanford University, Palo Alto, CA 94304-5592, USA.

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.

PMID:
22326585
PMCID:
PMC3501142
DOI:
10.1016/j.humimm.2012.01.004
[Indexed for MEDLINE]
Free PMC Article

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