Differences in clinical and genetic characteristics between early- and late-onset narcolepsy in a Han Chinese cohort.

Early- and late-onset narcolepsy constitutes two distinct diagnostic subgroups. However, it is not clear whether symptomology and genetic risk factors differ between early- and late-onset narcoleptics. This study compared clinical data and single-nucleotide polymorphisms (SNPs) between early- and late-onset patients in a large cohort of 899 Han Chinese narcolepsy patients. Blood, cerebrospinal fluid, and clinical data were prospectively collected from patients, and patients were genotyped for 40 previously reported narcolepsy risk-conferring SNPs. Genetic risk scores (GRSs), associations of five different sets of SNPs (GRS1-GRS5) with early- and late-onset narcolepsy, were evaluated using logistic regression and receiver operating characteristic curves. Mean sleep latency was significantly shorter in early-onset cases than in late-onset cases. Symptom severity was greater among late-onset patients, with higher rates of sleep paralysis, hypnagogic hallucinations, health-related quality of life impairment, and concurrent presentation with four or more symptoms. Hypocretin levels did not differ significantly between early- and late-onset cases. Only rs3181077 (CCR1/CCR3) and rs9274477 (HLA-DQB1) were more prevalent among early-onset cases. Only GRS1 (26 SNPs; OR = 1.513, 95% CI: 0.893-2.585; P < 0.05) and GRS5 (6 SNPs; OR = 1.893, 95% CI: 1.204-2.993; P < 0.05) were associated with early-onset narcolepsy, with areas under the receiver operating characteristic curves of 0.731 and 0.732, respectively. Neither GRS1 nor GRS5 included SNPs in HLA regions. Our results indicate that symptomology and genetic risk factors differ between early- and late-onset narcolepsy. This protocol was approved by the Institutional Review Board (IRB) Panels on Medical Human Subjects at Peking University People's Hospital, China (approval No. Yuanlunshenlinyi 86) in October 2011.

Relationship between T-cell receptor α gene polymorphisms and symptomatic differences in patients with narcolepsy type 1.

BACKGROUND: Recent genome-wide association studies have identified an important role of T-cell receptor α (TRA) gene in the development of narcolepsy type 1. However, the role of TRA haplotype polymorphisms in the symptomatic diversity of narcolepsy remains unclear. This study aimed to investigate whether TRA polymorphisms can influence the symptomatic diversity of narcolepsy. METHODS: Totally, 903 patients with narcolepsy type 1 were included in the study. Patients were divided into different groups according to their symptoms. First, 13 genotyped single nucleotide polymorphisms in the TRA were assessed for their association with symptoms of narcolepsy. We used the Chi-square test to determine differences in genotype frequencies in patients with narcolepsy. Further, we identified the haplotypes and variations of the TRA and tested their association with the symptoms of narcolepsy using a logistic regression model. RESULTS: According to the results of the logistic regression, TRA haplotypes TG and CT were significantly associated with auditory hallucination, with odds ratios of 1.235 (95% confidence interval [CI], 1.012-1.507) and 1.236 (95% CI, 1.012-1.511), respectively (P < 0.05). CONCLUSIONS: The patterns of haplotype in TRA (haplotypes TG and CT) are associated with hypnagogic auditory hallucination in patients with narcolepsy type 1. However, further studies are needed to confirm our results and explore the underlying mechanisms.