Crooks Súsanna A, Bech Sára, Halling Jónrit, Christiansen Debes H, Ritz Beate, Petersen Maria Skaalum
Department of Occupational Medicine and Public Health, The Faroese Hospital System, Tórshavn, Faroe Islands.
Department of Occupational Medicine and Public Health, The Faroese Hospital System, Tórshavn, Faroe Islands; Department of Neurology, Copenhagen University Hospital, Bispebjerg, Copenhagen, Denmark.
Neurosci Lett. 2018 May 14;675:116-119. doi: 10.1016/j.neulet.2018.03.064. Epub 2018 Mar 31.
Mitochondrial dysfunction, oxidative stress and energy production have been implicated in the etiology of Parkinson's disease (PD). Several agents are under investigation for potential neuroprotective effects including acetyl-l-carnitine (ALC).
To investigate whether low carnitine levels and mutations in the SLC22A5 gene encoding the carnitine transporter are associates with PD risk in the Faroe Islands where the prevalence of both PD and carnitine transporter deficiency (CTD) is high.
We conducted a case-control study with 121 cases and 235 randomly selected controls, matched by gender and age. Blood spots were analyzed for free and total carnitine levels by QUATTRO LC triple quadrupole mass spectrometry (MS/MS) and sequencing performed for five genetic mutations in the SLC22A5 gene with ABI PRISM 3130.
PD cases had significantly lower levels of free and total carnitine levels compared with controls (P < .001). However, stratifying according to mutation status, the lower levels of carnitine was only evident among the non-mutation carriers. Specifically, no difference was found in c.95A > G mutation frequency in the SLC22A5 gene among cases and controls (p = .70).
Low carnitine levels seem to be associated with PD, but only in individuals without the c.95A > G mutation rendering the carnitine transporter less efficient. Thus, the difference in carnitine levels is not caused by a higher frequency of c.95A > G mutation carriers in cases. The cause may be dietary or due to different gut microbiota among cases.
线粒体功能障碍、氧化应激和能量产生与帕金森病（PD）的病因有关。包括乙酰左旋肉碱（ALC）在内的几种药物正在接受潜在神经保护作用的研究。
在法罗群岛，帕金森病和肉碱转运体缺乏症（CTD）的患病率都很高，研究低肉碱水平和编码肉碱转运体的SLC22A5基因突变是否与帕金森病风险相关。
我们进行了一项病例对照研究，有121例病例和235例随机选择的对照，按性别和年龄匹配。通过QUATTRO LC三重四极杆质谱（MS/MS）分析血斑中的游离和总肉碱水平，并使用ABI PRISM 3130对SLC22A5基因的五个基因突变进行测序。
与对照组相比，帕金森病病例的游离和总肉碱水平显著较低（P <.001）。然而，根据突变状态分层，较低的肉碱水平仅在非突变携带者中明显。具体而言，病例组和对照组中SLC22A5基因c.95A>G突变频率没有差异（p =.70）。
低肉碱水平似乎与帕金森病有关，但仅在没有c.95A>G突变的个体中，该突变会使肉碱转运体效率降低。因此，病例组中肉碱水平的差异不是由c.95A>G突变携带者的较高频率引起的。原因可能是饮食或病例组之间不同的肠道微生物群。
