HLA‐DQ association and allele competition in Chinese narcolepsy

In Japanese, Koreans and Caucasians, narcolepsy/hypocretin deficiency is tightly associated with the DRB1 * 15:01 ‐ DQA1 * 01:02 ‐ DQB1 * 06:02 haplotype. Studies in African‐Americans suggest a primary effect of DQB1 * 06:02 , but this observation has been difficult to confirm in other populations because of high linkage disequilibrium between DRB1 * 15:01/3 and DQB1 * 06:02 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 DQB1 * 06:02 positive. Comparing cases with 103 unselected controls, and 110 and 79 controls selected for the presence of DQB1 * 06:02 and DRB1 * 15:01 , we found that the presence of DQB1 * 06:02 and not DRB1 * 15:01 was associated with narcolepsy. In particular, Southern Chinese haplotypes such as the DRB1 * 15:01 ‐ DQA1 * 01:02 ‐ DQB1 * 06:01 and DRB1 * 15:01 ‐ DQA1 * 01:02 ‐ DQB1 * 05 were not associated with narcolepsy. As reported in Japanese, Koreans, African‐Americans and Caucasians, additional protective effects of DQA1 * 01 (non‐ DQA1 * 01:02 ) and susceptibility effects of DQB1 * 03:01 were observed. These results illustrate the extraordinary conservation of HLA class II effects in narcolepsy across populations and show that DRB1 * 15:01 has no effect on narcolepsy susceptibility in the absence of DQB1 * 06:02 . The results are also in line with a previously proposed ‘ HLA‐DQ allelic competition model’ that involves competition between non‐ DQA1 * 01:02 , non‐ DQB1 * 06:02 ‘competent’ (able to dimerize together) DQ1 alleles and the major DQ α*01:02 / DQ β*06:02 narcolepsy heterodimer to reduce susceptibility.