Emmanuel Mignot

Publication Details

  • HLA-DQ association and allele competition in Chinese narcolepsy TISSUE ANTIGENS Han, F., Lin, L., Li, J., Dong, S. X., An, P., Zhao, L., Liu, N. Y., Li, Q. Y., Yan, H., Gao, Z. C., Faraco, J., Strohl, K. P., Liu, X., Miyadera, H., Mignot, E. 2012; 80 (4): 328-335

    Abstract:

    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?*01:02/ DQ?*06:02 narcolepsy heterodimer to reduce susceptibility.

    View details for DOI 10.1111/j.1399-0039.2012.01948.x

    View details for Web of Science ID 000308938000005

    View details for PubMedID 22862152

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