HLA-DQA, HLA-DQB AND HLA-DRB ALLELE CONTRIBUTION TO NARCOLEPSY SUSCEPTIBILITY

The association of narcolepsy with HLA class I antigens and HLA class ii alleles was studied in a series of Spanish narcoleptic patients. Th e haplotype DRB11501-DRB5*0101-DQA1*0102-DQB1*0602 was found to be si gnificantly associated with the disease, while the haplotype DRB10701 -DRB401-DQA1*0201-DQB1*02 might confer a slight protective effect aga inst narcolepsy. Gene dose-effect was not seen in any of the involved alleles, and linkage disequilibrium between the positively associated alleles was found to be stronger in patients than in controls. Statist ical analysis applied to identify the HLA allele truly responsible for the association did not clearly discriminate between the contribution of DRB11501 and that of DQB1*0602, but it proved that the associatio n with DQA10102 is secondary to that with DRB1*1501/DQB1*0602. Analys is of the diagnostic value of typing for the narcolepsy-associated all eles demonstrated a very high negative predictive value and revealed t hat this test can be convenient for exclusion of narcolepsy in cases w hen the diagnosis is not evident after clinical evaluation and the mar ker haplotype is absent. Finally, a family study indicated that narcol epsy is a multifactorial disorder that involves HLA genes under an inc omplete penetrance model, with possible influences from environmental factors or other genes different to HLA genes.