Szolnoki Zoltan, Kondacs Andras, Mandi Yvette, Bodor Anita, Somogyvari Ferenc
Department of Cerebrovascular Diseases, Pándy Kálmán County Hospital, Békéscsaba, Pipacs köz 9, 5600, Gyula, Hungary.
Neuromolecular Med. 2009;11(2):101-5. doi: 10.1007/s12017-009-8071-4. Epub 2009 Jun 18.
Multiple sclerosis (MS), which results in damage of the white matter at multiple foci, poses a far-reaching public health problem in view of the burden it imposes on the affected young and middle-aged. Some previous data suggested that roles could be played in the demyelinization of the white matter of the brain by the malfunctioning of the mitochondria and mitochondria-associated reactive oxygen species. In this context, we hypothesized that the finely tuned dynamic stability of the mitochondrial membrane potential (MMP), which is the main mirror of the functional state of the mitochondria, is essential for the intact nature of the glia cells in the brain. Setting out from this, our aim in this study was to examine how the rs10807344 and rs2270450 genetic variants of mitochondrial uncoupling protein 4 (mUCP4) can give rise to the development of MS, since mUCP4 is presumed to be of great importance in the regulation of the MMP and cellular energy metabolism. The clinical and genetic data on 120 relapsing-remitting MS patients and 250 neuroimaging alteration-free subjects were analyzed. The rs10807344 CC genotype proved to exert a protective effect against the occurrence of MS (neuroimaging alteration-free controls, 58%; MS group, 33%; P < 0.0000089; OR, 0.32; 95% CI: 0.2-0.56, P < 0.005). The present findings indirectly raise the possibility that a shift or imbalance in the finally regulated MMP plays a role in the development of MS.
多发性硬化症（MS）会导致多个病灶处的白质受损，鉴于其给受影响的中青年带来的负担，这是一个影响深远的公共卫生问题。先前的一些数据表明，线粒体功能异常以及与线粒体相关的活性氧可能在大脑白质脱髓鞘过程中发挥作用。在此背景下，我们推测线粒体膜电位（MMP）的精细动态稳定性（这是线粒体功能状态的主要反映）对于大脑中神经胶质细胞的完整性质至关重要。基于此，我们在本研究中的目的是研究线粒体解偶联蛋白4（mUCP4）的rs10807344和rs2270450基因变异如何导致MS的发生，因为mUCP4被认为在MMP调节和细胞能量代谢中具有重要作用。分析了120例复发缓解型MS患者和250例无神经影像学改变的受试者的临床和遗传数据。结果证明，rs10807344 CC基因型对MS的发生具有保护作用（无神经影像学改变的对照组为58%；MS组为33%；P < 0.0000089；OR为0.32；95% CI：0.2 - 0.56，P < 0.005）。目前的研究结果间接提示，最终调节的MMP发生改变或失衡在MS的发展中起作用。
