High nocturnal sleep fragmentation is associated with low T lymphocyte P2[Y.sub.11] protein levels in narcolepsy type 1

Study Objectives: 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 P2[Y.sub.11...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Sleep (New York, N.Y.) N.Y.), 2021-08, Vol.44 (8), p.1
Hauptverfasser: Viste, Rannveig, Viken, Marte K, Lie, Benedicte A, Juvodden, Hilde T, Nordstrand, Sebjorg E.H, Thorsby, Per M, Rootwelt, Terje, Kornum, Birgitte R, Knudsen-Heier, Stine
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Study Objectives: 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 P2[Y.sub.11] protein levels in T lymphocytes in patients with NT1, their first-degree relatives and unrelated controls. Methods: 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 P2[Y.sub.11] protein levels were quantified using flow cytometry in 167 patients and relatives. Symptoms and sleep recording parameters were also collected. Results: We found an association between NT1 and the rs2305795 A allele (OR = 2, 95% CI (1.3, 3.0), p = 0.001). T lymphocyte P2[Y.sub.11] 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' P2[Y.sub.11] 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 P2[Y.sub.11] protein levels. Conclusions: 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 P2[Y.sub.11] protein levels. A high level of nocturnal sleep fragmentation was associated with low P2[Y.sub.11] levels in patients. This suggests that P2[Y.sub.11] has a previously unknown function in sleep-wake stabilization that affects the severity of NT1. Key words: narcolepsy 1; P2RY11; P2[Y.sub.11]; sleep fragmentation
ISSN:0161-8105
DOI:10.1093/sleep/zsab062