Norwegian Center of Expertise for Neurodevelopmental Disorders and Hypersomnias (NevSom), Department of Rare Disorders, Oslo University Hospital, Oslo, Norway.
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Sleep. 2021 Aug 13;44(8). doi: 10.1093/sleep/zsab062.
Narcolepsy type 1 (NT1) is associated with hypocretin neuron loss. However, there are still unexplained phenotypic NT1 features. We investigated the associations between clinical and sleep phenotypic characteristics, the NT1-associated P2RY11 polymorphism rs2305795, and P2Y11 protein levels in T lymphocytes in patients with NT1, their first-degree relatives and unrelated controls.
The P2RY11 SNP was genotyped in 100 patients (90/100 H1N1-(Pandemrix)-vaccinated), 119 related and 123 non-related controls. CD4 and CD8 T lymphocyte P2Y11 protein levels were quantified using flow cytometry in 167 patients and relatives. Symptoms and sleep recording parameters were also collected.
We found an association between NT1 and the rs2305795 A allele (OR = 2, 95% CI (1.3, 3.0), p = 0.001). T lymphocyte P2Y11 protein levels were significantly lower in patients and relatives homozygous for the rs2305795 risk A allele (CD4: p = 0.012; CD8: p = 0.007). The nocturnal sleep fragmentation index was significantly negatively correlated with patients' P2Y11 protein levels (CD4: p = 0.004; CD8: p = 0.006). Mean MSLT sleep latency, REM-sleep latency, and core clinical symptoms were not associated with P2Y11 protein levels.
We confirmed that the P2RY11 polymorphism rs2305795 is associated with NT1 also in a mainly H1N1-(Pandemrix)-vaccinated cohort. We demonstrated that homozygosity for the A risk allele is associated with lower P2Y11 protein levels. A high level of nocturnal sleep fragmentation was associated with low P2Y11 levels in patients. This suggests that P2Y11 has a previously unknown function in sleep-wake stabilization that affects the severity of NT1.
1 型发作性睡病（NT1）与下丘脑分泌素神经元缺失有关。然而，仍有一些无法解释的 NT1 表型特征。我们研究了 NT1 患者、一级亲属和无关对照者的临床和睡眠表型特征、与 NT1 相关的 P2RY11 多态性 rs2305795 以及 T 淋巴细胞中 P2Y11 蛋白水平之间的关联。
在 100 例患者（90/100 例接受 H1N1-（Pandemrix）-疫苗接种）、119 例相关和 123 例无关对照中，对 P2RY11 SNP 进行了基因分型。使用流式细胞术对 167 例患者和亲属的 CD4 和 CD8 T 淋巴细胞 P2Y11 蛋白水平进行了定量。还收集了症状和睡眠记录参数。
我们发现 NT1 与 rs2305795 A 等位基因（OR=2，95%CI（1.3，3.0），p=0.001）有关。rs2305795 风险 A 等位基因纯合的患者和亲属的 T 淋巴细胞 P2Y11 蛋白水平显著降低（CD4：p=0.012；CD8：p=0.007）。夜间睡眠碎片化指数与患者的 P2Y11 蛋白水平呈显著负相关（CD4：p=0.004；CD8：p=0.006）。平均 MSLT 睡眠潜伏期、REM 睡眠潜伏期和核心临床症状与 P2Y11 蛋白水平无关。
我们在主要接受 H1N1-（Pandemrix）-疫苗接种的队列中证实，P2RY11 多态性 rs2305795 与 NT1 也有关。我们证明，A 风险等位基因纯合与 P2Y11 蛋白水平降低有关。夜间睡眠碎片化程度较高与患者的 P2Y11 水平较低有关。这表明 P2Y11 在睡眠-觉醒稳定中具有未知的功能，影响 NT1 的严重程度。
