HLA-DQ association and allele competition in Chinese narcolepsy.

In Japanese, Koreans and Caucasians, narcolepsy/hypocretin deficiency is tightly associated with the DRB115:01-DQA101:02-DQB106:02 haplotype. Studies in African-Americans suggest a primary effect of DQB106:02, but this observation has been difficult to confirm in other populations because of high linkage disequilibrium between DRB115:01/3 and DQB106:02 in most populations. In this study, we studied human leucocyte antigen (HLA) class II in 202 Chinese narcolepsy patients (11% from South China) and found all patients to be DQB106:02 positive. Comparing cases with 103 unselected controls, and 110 and 79 controls selected for the presence of DQB106:02 and DRB115:01, we found that the presence of DQB106:02 and not DRB115:01 was associated with narcolepsy. In particular, Southern Chinese haplotypes such as the DRB115:01-DQA101:02-DQB106:01 and DRB115:01-DQA101:02-DQB105 were not associated with narcolepsy. As reported in Japanese, Koreans, African-Americans and Caucasians, additional protective effects of DQA101 (non-DQA101:02) and susceptibility effects of DQB103:01 were observed. These results illustrate the extraordinary conservation of HLA class II effects in narcolepsy across populations and show that DRB115:01 has no effect on narcolepsy susceptibility in the absence of DQB106:02. The results are also in line with a previously proposed 'HLA-DQ allelic competition model' that involves competition between non-DQA101:02, non-DQB106:02 'competent' (able to dimerize together) DQ1 alleles and the major DQα01:02/ DQβ06:02 narcolepsy heterodimer to reduce susceptibility.