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論文
- タイトル
- タイトル（英）
- Low carnitine palmitoyltransferase1 activity is a risk factor for narcolepsy type 1 and other hypersomnia.
- 参照URL
- https://researchmap.jp/narcolepsy/published_papers/38497469
- 著者
- 著者（英）
- Makoto Honda,Yosuke Shigematsu,Mihoko Shimada,Yoshiko Honda,Katsushi Tokunaga,Taku Miyagawa
- 担当区分
- 概要
- 概要（英）
- STUDY OBJECTIVES: Narcolepsy type 1 (NT1) is associated with metabolic abnormalities but their etiology remains largely unknown. The gene for carnitine palmitoyltransferase 1B (CPT1B) and abnormally low serum acylcarnitine level have been linked to NT1. To elucidate the details of altered fatty acid metabolism, we determined levels of individual acylcarnitines and evaluated CPT1 activity in patients with NT1 and other hypersomnia. METHODS: Blood samples from 57 NT1, 51 other hypersomnia patients and 61 healthy controls were analyzed. The levels of 25 major individual acylcarnitines were determined and the C0/(t[C16]+t[C18]) ratio was used as a CPT1 activity marker. We further performed transcriptome analysis using independent blood samples from 42 NT1 and 42 healthy controls to study the relevance of fatty acid metabolism. NT1 specific changes in CPT1 activity and in expression of related genes were investigated. RESULTS: CPT1 activity was lower in patients with NT1 (p = 0.00064) and other hypersomnia (p = 0.0014) than in controls. Regression analysis revealed that CPT1 activity was an independent risk factor for NT1 (OR: 1.68; p = 0.0031) and for other hypersomnia (OR: 1.64; p = 0.0042).There was a significant interaction between obesity (BMI <25, ≥25) and the SNP rs5770917 status such that non-obese NT1 patients without risk allele had better CPT1 activity (p=0.0089) The expression levels of carnitine-acylcarnitine translocase (CACT) and CPT2 in carnitine shuttle were lower in NT1.(p=0.000051 and p=0.00014 respectively). CONCLUSIONS: These results provide evidences that abnormal fatty acid metabolism is involved in the pathophysiology of NT1 and other hypersomnia.
- 出版者・発行元
- 出版者・発行元（英）
- 誌名
- 誌名（英）
- Sleep
- 巻
- 号
- 開始ページ
- 終了ページ
- 出版年月
- 2022年7月10日
- 査読の有無
- 査読有り
- 招待の有無
- 掲載種別
- 研究論文（学術雑誌）
- ISSN
- DOI URL
- https://doi.org/10.1093/sleep/zsac160
- 共同研究・競争的資金等の研究課題