Abnormally Low Serum Acylcarnitine Levels in Narcolepsy Patients
Abnormally Low Serum Acylcarnitine Levels in Narcolepsy Patients
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DOI：
10.1093/sleep/34.3.349
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发表时间：
2011-03-01
期刊：
影响因子：
5.6
通讯作者：
Honda, Makoto
中科院分区：
文献类型：
--
作者：
Miyagawa, Taku;Miyadera, Hiroko;Honda, Makoto
背景：发作性睡病是一种以白天过度嗜睡、猝倒和快速眼动睡眠异常为特征的睡眠障碍。一项全基因组关联研究发现了一种新的嗜睡相关单核苷酸多态性（SNP），rs5770917，位于CPT 1B（肉毒碱棕榈酰转移酶1B）附近。在这项研究中，我们分析了CPT 1B的表达水平，并测量了从嗜睡症患者和对照受试者的血液样本中的肉毒碱分数，以测试的假设，脂肪酸β-氧化改变narcoleps.Methodology和结果：我们测量了CPT 1B的mRNA表达在白色血细胞的38发作性睡病患者和56名健康对照。血清肉毒碱分数（总肉毒碱，游离肉毒碱，和酰基肉毒碱）测定在38发作性睡病患者和30 56名对照组。逐步多元回归分析显示，SNP rs5770917的危险等位基因（C）与CPT 1B mRNA表达降低显著相关（P = 1.0 × 10 - 9），发作性睡病患者CPT 1B表达高于对照组（P = 0.005）。21%的发作性睡病患者的酰基肉毒碱水平异常低，而所有对照组的酰基肉毒碱水平均在正常范围内。多元逐步回归分析显示，发作性睡病的诊断与血清酰基肉碱水平异常降低有关（P = 0.006），而CPT1B表达水平和BMI与血清酰基肉碱水平异常降低无关（P = 0.006）。在发作性睡病中观察到的酰基肉毒碱水平异常低表明脂肪酸β-氧化途径功能障碍。
Background: Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness, cataplexy, and REM sleep abnormalities. A genome-wide association study identified a novel narcolepsy-related single nucleotide polymorphism (SNP), rs5770917, which is located adjacent to CPT1B (carnitine palmitoyltransferase 1B). In this study, we analyzed the CPT1B expression level and measured the carnitine fractions in blood samples obtained from narcolepsy patients and control subjects to test the hypothesis that fatty acid beta-oxidation is altered in narcolepsy.Methodology and Results: We measured CPT1B mRNA expression in white blood cells of 38 narcolepsy patients and 56 healthy control subjects. The serum carnitine fractions (total carnitine, free carnitine, and acylcarnitine) were measured in the 38 narcolepsy patients and in 30 of 56 control subjects. Stepwise multiple regression analysis revealed that the risk allele (C) for SNP rs5770917 was significantly associated with decreased CPT1B mRNA expression (P = 1.0 x 10(-9)), and the CPT1B expression was higher in the narcolepsy patients than in the controls (P = 0.005). The acylcarnitine levels were abnormally low in 21% of the narcolepsy patients while those of all the controls were within the normal range. Stepwise multiple regression analysis using the dichotomous variable for acylcarnitine (normal or abnormal) as an objective variable revealed that the diagnosis of narcolepsy but not CPT1B expression level and BMI was associated with abnormally low acylcarnitine levels (P = 0.006).Conclusions: Our results indicate that multiple factors are involved in the regulation of serum acylcarnitine levels. Abnormally low levels of acylcarnitine observed in narcolepsy suggest dysfunctional fatty acid beta-oxidation pathway.