Department of Pulmonary Medicine, Peking University People's Hospital, Beijing, China.
Sleep Med. 2012 Mar;13(3):269-72. doi: 10.1016/j.sleep.2011.06.020. Epub 2011 Dec 15.
Polymorphisms in the TCRA and P2RY11, two immune related genes, are associated with narcolepsy in Caucasians and Asians. In contrast, CPT1B/CHKB polymorphisms have only been shown to be associated with narcolepsy in Japanese, with replication in a small group of Koreans. Our aim was to study whether these polymorphisms are associated with narcolepsy and its clinical characteristics in Chinese patients with narcolepsy.
We collected clinical data on 510 Chinese patients presenting with narcolepsy/hypocretin deficiency. Patients were included either when hypocretin deficiency was documented (CSF hypocretin-1≤110 pg/ml, n=91) or on the basis of the presence of clear cataplexy and HLA-DQB1∗0602 positivity (n=419). Genetic data was compared to typing obtained in 452 controls matched for geographic origin within China. Clinical evaluations included demographics, the Stanford Sleep Inventory (presence and age of onset of each symptom), and Multiple Sleep Latency Test (MSLT) data.
Chinese narcolepsy was strongly and dose dependently associated with TCRA (rs1154155C) and P2RY11 (rs2305795A) but not CPT1B/CHKB (rs5770917C) polymorphisms. CPT1B/CHKB polymorphisms were not associated with any specific clinical characteristics. TCRA rs1154155A homozygotes (58 subjects) had a later disease onset, but this was not significant when corrected for multiple comparisons, thus replication is needed. CPT1B/CHKB or P2RY11 polymorphisms were not associated with any specific clinical characteristics.
The study extends on the observation of a strong multiethnic association of polymorphisms in the TCRA and P2RY11 with narcolepsy, but does not confirm the association of CPT1B/CHKB (rs5770917) in the Chinese population.
TCRA 和 P2RY11 这两个免疫相关基因中的多态性与白种人和亚洲人嗜睡症有关。相比之下，CPT1B/CHKB 多态性仅与日本人的嗜睡症有关，在一小部分韩国人中也得到了复制。我们的目的是研究这些多态性是否与中国嗜睡症患者的嗜睡症及其临床特征有关。
我们收集了 510 名中国嗜睡症/下丘脑分泌素缺乏症患者的临床数据。患者分为下丘脑分泌素缺乏症患者（CSF 下丘脑分泌素-1≤110pg/ml，n=91）或根据明确的猝倒症和 HLA-DQB1∗0602 阳性（n=419）纳入。将遗传数据与在中国同一地理起源的 452 名对照者的基因分型进行比较。临床评估包括人口统计学、斯坦福睡眠量表（每种症状的出现和发病年龄）和多次睡眠潜伏期试验（MSLT）数据。
中国嗜睡症与 TCRA（rs1154155C）和 P2RY11（rs2305795A）呈强烈且剂量依赖性相关，但与 CPT1B/CHKB（rs5770917C）多态性无关。CPT1B/CHKB 多态性与任何特定的临床特征无关。TCRA rs1154155A 纯合子（58 例）发病较晚，但在进行多次比较校正后并不显著，因此需要进一步验证。CPT1B/CHKB 或 P2RY11 多态性与任何特定的临床特征无关。
本研究扩展了 TCRA 和 P2RY11 多态性与嗜睡症的多民族强相关性观察，但在中国人群中未证实 CPT1B/CHKB（rs5770917）的相关性。
