Narcolepsy and the HLA System

Abstract
In the second part of their review of the HLA system (Sept. 14 issue),1 Klein and Sato state that the HLA class II association in human narcolepsy is due to linkage disequilibrium with mutations in the gene coding for the hypocretin type 2 receptor (HCRTR2). HCRTR2 is located on human chromosome 6, but at a very large genetic distance from the HLA loci; there is no linkage disequilibrium between the HLA alleles and HCRTR2 over a distance of more than 30 million base pairs and 33.4 centimorgans. However, there is a different association between narcolepsy and the HLA system. Microsatellite-marker and sequencing studies of the HLA class II region have shown that HLA-DQ is the primary susceptibility locus for human narcolepsy in the HLA region.2-4