Association analysis of the major histocompatibility complex, class II, DQ β1 gene, HLA-DQB1, with narcolepsy in Han Chinese patients from Taiwan

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. 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. 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. 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.