DQB1*0301 and DQB1*0601 Modulate Narcolepsy Susceptibility in Koreans
| Autor: | Jong-Hyun Jeong, Betty Lo, Jing Zhang, John A. Hansen, Yong-Sil Kweon, Seung Chul Hong, Yoon Kyung Shin, F. Carl Grumet, Su-Yeon Kim, Ling Lin, Emmanuel Mignot, Anajane G. Smith, Mali Einen |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
musculoskeletal diseases
medicine.medical_specialty Linkage disequilibrium endocrine system diseases Cataplexy Immunology Population Context (language use) Compound heterozygosity HLA-DQ alpha-Chains immune system diseases HLA-DQ Antigens Internal medicine HLA-DQ beta-Chains Humans Immunology and Allergy Medicine Genetic Predisposition to Disease skin and connective tissue diseases education Narcolepsy education.field_of_study Korea Membrane Glycoproteins business.industry nutritional and metabolic diseases General Medicine Odds ratio medicine.disease Orexin Endocrinology medicine.symptom business |
| Zdroj: | Human Immunology. 68:59-68 |
| ISSN: | 0198-8859 |
| DOI: | 10.1016/j.humimm.2006.10.006 |
| Popis: | The association of narcolepsy with HLA-DQB1*0602 is established in Japanese, African-Americans, European, and North American Caucasians. We examined DRB1, DRB3, DRB4, DRB5, DQA1, and DQB1 in 163 patients with centrally mediated daytime sleepiness (100 with narcolepsy) and 211 Korean controls. In this population, the DQB1*0602 association was always evident in the context of the DRB1*1501-DQA1*0102-DQB1*0602 haplotype. The DQB1*0602 association was highest in cases with hypocretin deficiency (100% vs 13% in controls), most of which had narcolepsy-cataplexy (81%). A weaker DQB1*0602 (45%) association was present in cases without cataplexy. No human leukocyte antigen (HLA) association was present in idiopathic hypersomnia or in cases with normal cerebrospinal fluid (CSF) hypocretin-1. As in other populations, DQB1*0602 homozygosity increased risk in cases with cataplexy and/or hypocretin deficiency (odds ratio = 2.0 vs heterozygotes). Non-DQB1*0602 allelic effects were also observed but could not be interpreted in the context of DQB1*0602 overabundance and linkage disequilibrium. We therefore next analyzed compound heterozygote effects in 77 subjects with either hypocretin deficiency or cataplexy and one copy of DRB1*1501-DQA1*0102-DQB1*0602, a sample constructed to maximize etiologic homogeneity. In this analysis, we found additional predisposing effects of DQB1*0301 and protective effects for DQA1*0103-DQB1*0601. Unexpectedly, the predisposing effects of DQB1*0301 were present in the context of various DQA1-bearing haplotypes. A predisposing effect of DQA1*0303 was also suggested. These results indicate a remarkable consistency in the complex HLA association present in narcolepsy across multiple ethnic groups. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect