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

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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 languageEnglish
JournalHuman Immunology
Issue number4
Pages (from-to)405-10
Number of pages6
Publication statusPublished - Apr 2012

    Research areas

  • 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

ID: 196168806