Dataset Information

Abnormally low serum acylcarnitine levels in narcolepsy patients.

ABSTRACT: 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 ?-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 × 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 ?-oxidation pathway.

SUBMITTER: Miyagawa T

PROVIDER: S-EPMC3041711 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Abnormally low serum acylcarnitine levels in narcolepsy patients.

Miyagawa Taku T Miyadera Hiroko H Tanaka Susumu S Kawashima Minae M Shimada Mihoko M Honda Yutaka Y Tokunaga Katsushi K Honda Makoto M

Sleep 20110301 3

<h4>Background</h4>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 t ...[more]

PMID: 21358852

Similar Datasets

Project description:BACKGROUND:Previously, we demonstrated up-regulated activated CD4+ and CD8+ T lymphocytes as well as up-regulated cytotoxic NK cells in the blood of patients with idiopathic recurrent miscarriage. In the present study, we tried to identify deficiencies in counter-regulating immune mechanisms of these patients. METHOD:Cytokines were determined in NK cells and in plasma samples of 35 healthy controls, 33 patients with idiopathic recurrent miscarriage, 34 patients with end stage renal disease, 10 transplant patients early and 37 transplant patients late post-transplant using flow-cytometry and luminex. In addition, cytokines were studied in supernatants of cell cultures with peripheral blood mononuclear cells stimulated in-vitro with tumor cell line K562. RESULTS:Patients with idiopathic recurrent miscarriage exhibited the highest absolute cell counts of circulating TGFß1+ NK, NKT and T lymphocytes and the lowest TGFß1 plasma levels of all study groups (for all p < 0.050). In-vitro, peripheral blood mononuclear cells of patients with idiopathic recurrent miscarriage showed high spontaneous TGFß1 production that could not be further increased by stimulation with K562, indicating increased consumption of TGFß1 by activated cells in the cell culture. Moreover, patients with idiopathic recurrent miscarriage had abnormally high IL4+ as well as abnormally high IFNy+ NK cells (p < 0.010) but similar IL10+ NK cell numbers as female healthy controls and showed the lowest plasma levels of IL10, TGFß3, IL1RA, IL1ß, IL5, IL6, IL8, IL17, TNFα, GM-CSF, TPO and VEGF and the highest plasma levels of G-CSF, FGF-basic, CCL3 and CXCL5 as compared to female HC and female transplant recipients (for all p < 0.050). CONCLUSIONS:Patients with idiopathic recurrent miscarriage show an activated immune system that can hardly be stimulated further and cannot be efficiently down-regulated by up-regulated TGFß1+ and IL4+ NK, NKT and T lymphocytes which are present concomitantly in these patients. The strongly decreased TGFß and IL10 plasma levels indicate deficient down-regulation and reflect a dysbalance of the immune system in patients with idiopathic recurrent miscarriage. These findings may be relevant for explaining the pathogenesis of idiopathic recurrent miscarriage.

Dataset Information

Abnormally low serum acylcarnitine levels in narcolepsy patients.

Publications

Abnormally low serum acylcarnitine levels in narcolepsy patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets