High nocturnal sleep fragmentation is associated with low T lymphocyte P2Y11protein levels in narcolepsy type 1

Research output: Contribution to journalJournal articleResearchpeer-review

  • Rannveig Viste
  • Marte K. Viken
  • Benedicte A. Lie
  • Hilde T. Juvodden
  • Sebjørg E.H. Nordstrand
  • Per M. Thorsby
  • Terje Rootwelt
  • Kornum, Birgitte Rahbek
  • Stine Knudsen-Heier

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 P2Y11 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 P2Y11 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 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. 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 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.

Original languageEnglish
Article numberzsab062
Issue number8
Number of pages12
Publication statusPublished - 2021

Bibliographical note

Publisher Copyright:
© 2021 Sleep Research Society 2021. Published by Oxford University Press on behalf of the Sleep Research Society.

    Research areas

  • narcolepsy 1, P2RY11, P2Y, sleep fragmentation

ID: 279888462