Sleep Institute, University of Washington, Seattle, WA 98104-2499, USA.
Sleep. 2010 Jan;33(1):29-35. doi: 10.1093/sleep/33.1.29.
To investigate associations between HLA-DQB1*0602 allele status and measures of narcolepsy symptom severity.
Cross-sectional study of population-based narcolepsy patients.
King County, Washington.
All prevalent cases (n = 279) of physician-diagnosed narcolepsy ascertained from 2001-2005.
N/A.
Narcolepsy diagnosis was based on cataplexy status, diagnostic sleep study results, and chart review. The number of HLA-DQB1 alleles was determined from buccal genomic DNA. Symptom severity instruments included the Epworth Sleepiness Scale (ESS), the Ullanlinna Narcolepsy Scale (UNS), age of symptom onset, subjective sleep latency and duration, and various clinical sleep parameters. We used linear regression adjusted for African American race and an extended chi-square test of trend to assess relationships across ordered groups defined by allele number (0, 1, or 2).
Narcolepsy patients were 63% female and 82% Caucasian, with a mean age of 47.6 years (SD = 17.1). One hundred forty-one (51%) patients had no DQB10602 alleles; 117 (42%) had one; and 21 (7%) had two. In the complete narcolepsy sample after adjustment for African American race, we observed a linear relationship between HLA-DQB10602 frequency and sleepiness as defined by the ESS (P < 0.01), narcolepsy severity as defined by UNS (P < 0.001), age of symptom onset (P < 0.05), and sleep latency (P < 0.001). In univariate analyses, HLA-DQB1*0602 frequency was also associated with napping (P < 0.05) and increased car and work accidents or near accidents (both P < 0.01). Habitual sleep duration was not associated with HLA status. These race-adjusted associations remained for the ESS (P < 0.05), UNS (P < 0.01), and sleep latency (P < 0.001) when restricting to narcolepsy with cataplexy.
Narcolepsy symptom severity varies in a linear manner according to HLA-DQB1*0602 allele status. These findings support the notion that HLA-DQ is a disease-modifying gene.
探讨人类白细胞抗原-DQB1*0602 等位基因状态与嗜睡症严重程度指标之间的关系。
基于人群的嗜睡症患者的横断面研究。
华盛顿州金县。
2001 年至 2005 年期间通过医生诊断确定的所有 279 例普遍性嗜睡症患者。
无。
嗜睡症的诊断基于猝倒状态、诊断性睡眠研究结果和图表审查。通过口腔基因组 DNA 确定 HLA-DQB1 等位基因的数量。症状严重程度的评估工具包括 Epworth 嗜睡量表（ESS）、Ullanlinna 嗜睡症量表（UNS）、症状发病年龄、主观睡眠潜伏期和持续时间以及各种临床睡眠参数。我们使用线性回归调整了非裔美国人的种族，并使用扩展的卡方趋势检验来评估按等位基因数量（0、1 或 2）定义的有序组之间的关系。
嗜睡症患者中 63%为女性，82%为白种人，平均年龄为 47.6 岁（标准差=17.1）。141 名（51%）患者没有 HLA-DQB10602 等位基因；117 名（42%）有一个；21 名（7%）有两个。在调整了非裔美国人种族后的完整嗜睡症样本中，我们观察到 HLA-DQB10602 频率与 ESS 定义的嗜睡（P<0.01）、UNS 定义的嗜睡症严重程度（P<0.001）、症状发病年龄（P<0.05）和睡眠潜伏期（P<0.001）之间存在线性关系。在单变量分析中，HLA-DQB1*0602 频率也与午睡（P<0.05）以及增加的汽车和工作事故或接近事故（均 P<0.01）相关。习惯性睡眠时间与 HLA 状态无关。当限制为伴有猝倒的嗜睡症时，这些经过种族调整的关联仍然存在于 ESS（P<0.05）、UNS（P<0.01）和睡眠潜伏期（P<0.001）中。
嗜睡症的严重程度与 HLA-DQB1*0602 等位基因状态呈线性变化。这些发现支持 HLA-DQ 是一种疾病修饰基因的观点。
