title: HLA-DQ association and allele competition in Chinese narcolepsy.
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 DQα*01:02/ DQβ*06:02 narcolepsy heterodimer to reduce susceptibility.
authors.affiliation: Department of Pulmonary Medicine, Beijing University People's Hospital, Beijing, China. hanfang1@hotmail.com
authors.forename: F
authors.initials: F
authors.lastname: Han
authors.forename: L
authors.initials: L
authors.lastname: Lin
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: S X
authors.initials: SX
authors.lastname: Dong
authors.forename: P
authors.initials: P
authors.lastname: An
authors.forename: L
authors.initials: L
authors.lastname: Zhao
authors.forename: N Y
authors.initials: NY
authors.lastname: Liu
authors.forename: Q Y
authors.initials: QY
authors.lastname: Li
authors.forename: H
authors.initials: H
authors.lastname: Yan
authors.forename: Z C
authors.initials: ZC
authors.lastname: Gao
authors.forename: J
authors.initials: J
authors.lastname: Faraco
authors.forename: K P
authors.initials: KP
authors.lastname: Strohl
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.forename: H
authors.initials: H
authors.lastname: Miyadera
authors.forename: E
authors.initials: E
authors.lastname: Mignot
mesh_terms: D000293:Adolescent; D044466:Asian People / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D059866:HLA-DQ beta-Chains / Q000235:genetics* / Q000378:metabolism; D059811:HLA-DRB1 Chains / Q000235:genetics* / Q000378:metabolism; D006239:Haplotypes; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics; D015810:Linkage Disequilibrium; D008297:Male; D009290:Narcolepsy / Q000235:genetics* / Q000378:metabolism; D009479:Neuropeptides / Q000172:deficiency / Q000235:genetics; D000068797:Orexins; D055503:Protein Multimerization; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains; C489631:HLA-DRB1*15:01 antigen; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins