Genetic Predisposition to Multiple Sleep Disorders Narcolepsy, Sleep Apnea, and Epilepsy: A Comprehensive Investigation of Risk Factors and Pathways
DOI:
https://doi.org/10.58445/rars.586Keywords:
Interleukin, Amyloid Beta Precursor Protein, Hypocretin Neuropeptide Precursor, Hypoxia Inducible Factor-1α, Narcolepsy, Sleep Apnea, Epilepsy, RNA Expression, Sleep Disorders, PredispositionAbstract
This project analyzes genomic and expression data in Narcolepsy and Sleep Apnea patients relating to specific genes of interest that link the 2 sleep disorders with Epilepsy. This research will help highlight groups of genes that can have various effects depending on where and what has mutated within. Shedding light on genes that can cause multiple disorders can open an area of research that is focused on understanding these mutations in more depth. To answer the question of whether there exists a genetic correlation between sleep disorders, I gathered genes from various databases and used MATLAB to search through the lists and compile genes that appeared in multiple different searches. I used MATLAB to narrow down genes that appeared in different searches within databases using certain keywords and used these matches to start research on what different mutations we know within these genes and their effects on sleep/risk for sleep disorders. I then determined whether there was a statistical difference between control and narcolepsy/sleep apnea patients through the expression of these certain groups of genes in patients with the aforementioned conditions. Although results showed that the Interleukin IL6 genes have no statistically different RNA expression differences within narcolepsy patients, suggesting the issue to be protein function over count. Within sleep apnea patients, IL10, IL27, and IL17 were interleukin genes that were statistically noteworthy. This study emphasizes the possible strong correlation between the IL genes (in addition to a couple other genes) and sleep conditions.
References
Blouin, Ashley M., et al. “Human Hypocretin and Melanin-Concentrating Hormone Levels Are Linked to Emotion and Social Interaction.” Nature Communications, vol. 4, 2013, p. 1547, https://doi.org/10.1038/ncomms2461.
Thannickal, Thomas C., et al. “Reduced Number of Hypocretin Neurons in Human Narcolepsy.” Neuron, vol. 27, no. 3, Sept. 2000, pp. 469–474, https://doi.org/10.1016/s0896-6273(00)00058-1.
Jones, Barbara E., and Oum K. Hassani. “The Role of Hcrt/Orx and MCH Neurons in Sleep-Wake State Regulation.” Sleep, vol. 36, no. 12, Dec. 2013, pp. 1769–72, https://doi.org/10.5665/sleep.3188. Accessed 16 Apr. 2020.
Konadhode, R. R., et al. “Optogenetic Stimulation of MCH Neurons Increases Sleep.” Journal of Neuroscience, vol. 33, no. 25, June 2013, pp. 10257–63, https://doi.org/10.1523/jneurosci.1225-13.2013.
[5] Neylan, Thomas C, et al. “Acute Cognitive Effects of the Hypocretin Receptor Antagonist Almorexant Relative to Zolpidem and Placebo: A Randomized Clinical Trial.” Sleep, vol. 43, no. 10, 18 Apr. 2020, https://doi.org/10.1093/sleep/zsaa080. Accessed 30 Nov. 2021.
[6] Tang, Bor Luen. “Amyloid Precursor Protein (APP) and GABAergic Neurotransmission.” Cells, vol. 8, no. 6, 6 June 2019, p. 550, https://doi.org/10.3390/cells8060550. Accessed 23 Oct. 2019.
Dauvilliers, Yves A., et al. “Hypocretin and Brain Î2-Amyloid Peptide Interactions in Cognitive Disorders and Narcolepsy.” Frontiers in Aging Neuroscience, vol. 6, 11 June 2014, https://doi.org/10.3389/fnagi.2014.00119.
Gabryelska, Agata, et al. “Relationship between HIF-1 and Circadian Clock Proteins in Obstructive Sleep Apnea Patients—Preliminary Study.” Journal of Clinical Medicine, vol. 9, no. 5, May 2020, p. 1599, https://doi.org/10.3390/jcm9051599. Accessed 11 Nov. 2021.
Gabryelska, Agata, et al. “Patients with Obstructive Sleep Apnea Present with Chronic Upregulation of Serum HIF-1α Protein.” Journal of Clinical Sleep Medicine, vol. 16, no. 10, Oct. 2020, pp. 1761–68, https://doi.org/10.5664/jcsm.8682. Accessed 11 Nov. 2021.
Cimmino, Flora, et al. “HIF-1 Transcription Activity: HIF1A Driven Response in Normoxia and in Hypoxia.” BMC Medical Genetics, vol. 20, no. 1, Feb. 2019, https://doi.org/10.1186/s12881-019-0767-1.
[11] Long, Qianfa, et al. “Hypoxia Inducible Factor-1α Expression Is Associated with Hippocampal Apoptosis during Epileptogenesis.” Brain Research, vol. 1590, Nov. 2014, pp. 20–30, https://doi.org/10.1016/j.brainres.2014.09.028. Accessed 8 Mar. 2023.
Li, Jie, et al. “Altered Expression of Hypoxia-Inducible Factor-1α Participates in the Epileptogenesis in Animal Models.” Synapse (New York, N.Y.), vol. 68, no. 9, 1 Sept. 2014, pp. 402–409, pubmed.ncbi.nlm.nih.gov/24889205/, https://doi.org/10.1002/syn.21752. Accessed 25 July 2023.
Uludag, Irem Fatma, et al. “IL-1β, IL-6 and IL1Ra Levels in Temporal Lobe Epilepsy.” Seizure, vol. 26, Mar. 2015, pp. 22–25, https://doi.org/10.1016/j.seizure.2015.01.009. Accessed 1 Apr. 2019.
Khalyfa, Abdelnaby, et al. “Genome-Wide Gene Expression Profiling in Children with Non-Obese Obstructive Sleep Apnea.” Sleep Medicine, vol. 10, no. 1, Jan. 2009, pp. 75–86, https://doi.org/10.1016/j.sleep.2007.11.006. Accessed 8 Jan. 2022.
Downloads
Posted
Categories
License
Copyright (c) 2023 Rhea Karthik
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.