title: Association analysis of the major histocompatibility complex, class II, DQ β1 gene, HLA-DQB1, with narcolepsy in Han Chinese patients from Taiwan.
abstract: BACKGROUND
  Narcolepsy is a rare, chronic, disabling neuropsychiatric disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, sleep paralysis, and abnormal rapid eye movement sleep. It is strongly associated with the HLA-DQB1(∗)06:02 allele in various ethnic groups. Our study aimed to investigate the allelic spectrum of HLA-DQB1 in a sample of Han Chinese patients with narcolepsy and control subjects from Taiwan.
  
  
  METHODS
  We determined the genotype of the major histocompatibility complex, class II, DQ β1 gene, HLA-DQB1, in 72 narcolepsy subjects (44 men, 28 women), including 52 narcolepsy subjects with cataplexy (narcolepsy+cataplexy), 20 narcolepsy subjects without cataplexy (narcolepsy-cataplexy), and 194 control subjects (94 men, 100 women) using a sequence-specific oligonucleotide-probe hybridization technique.
  
  
  RESULTS
  We found a strong HLA-DQB1(∗)06:02 association in narcolepsy+cataplexy subjects (odds ratio [OR], 321.4 [95% confidence interval {CI}, 70.7-1461.4]). The association was less prominent in narcolepsy-cataplexy subjects (OR, 6.9 [95% CI, 2.4-20.1]). In addition to the DQB1(∗)06:02, we found that (∗)03:01 also was a predisposing allele (OR, 2.0 [95% CI, 1.1-3.7]) in narcolepsy+cataplexy subjects, though the (∗)06:01 was a predisposing allele (OR, 2.8 [95% CI, 1.2-6.7]) in narcolepsy-cataplexy subjects. Furthermore, we found a significant overrepresentation of DQB1(∗)06:02 homozygotes in narcolepsy+cataplexy subjects.
  
  
  CONCLUSIONS
  Our data add further support to the strong association of the HLA-DQB1(∗)06:02 allele with narcolepsy, especially in narcolepsy+cataplexy patients. Our study also indicates additional HLA-DQB1 alleles may modify the presentation of narcolepsy+cataplexy patients, such as DQB1(∗)03:01 and DQB1(∗)06:01 in our study. Our results are limited by the small sample size and can only be considered as preliminary findings.
authors.affiliation: Center for Neuropsychiatric Research, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Yun-Hsiang
authors.initials: YH
authors.lastname: Chen
authors.forename: Yu-Shu
authors.initials: YS
authors.lastname: Huang
authors.forename: Wei-Hsien
authors.initials: WH
authors.lastname: Chien
authors.forename: Chia-Hsiang
authors.initials: CH
authors.lastname: Chen
mesh_terms: D044466:Asian People / Q000235:genetics* / Q000706:statistics & numerical data*; D002385:Cataplexy / Q000208:ethnology / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D059866:HLA-DQ beta-Chains / Q000235:genetics*; D019382:Human Growth Hormone; D006801:Humans; D008297:Male; D009290:Narcolepsy / Q000208:ethnology* / Q000235:genetics*; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology
chemical_list: D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D019382:Human Growth Hormone
keywords: Association; Cataplexy; Genetics; Human leukocyte antigen (HLA); Narcolepsy; Pathogenesis