Mamah Catherine E, Lesnick Timothy G, Lincoln Sarah J, Strain Kari J, de Andrade Mariza, Bower James H, Ahlskog J Eric, Rocca Walter A, Farrer Matthew J, Maraganore Demetrius M
Department of Neurology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
Ann Neurol. 2005 Mar;57(3):439-43. doi: 10.1002/ana.20387.
To determine whether the microtubule-associated protein tau (MAPT) and alpha-synuclein (SNCA) genes interact to confer Parkinson's disease (PD) susceptibility, we conducted a study of 557 case-control pairs. There was an increased risk of PD for persons with either SNCA 261/261 or MAPT H1/H1 genotypes as compared with persons with neither (odds ratio, 1.96; 95% confidence interval, 1.34-2.86; p = 0.0003). However, the combined effect of the two genotypes was the same as for either of the genotypes alone (separate and equal). These findings are consistent with in vitro experiments that revealed tau-mediated fibrillization of alpha-synuclein protein at low concentrations (dose threshold effect).
为了确定微管相关蛋白tau（MAPT）基因和α-突触核蛋白（SNCA）基因是否相互作用以赋予帕金森病（PD）易感性，我们对557对病例对照进行了研究。与两种基因型都没有的人相比，携带SNCA 261/261或MAPT H1/H1基因型的人患PD的风险增加（优势比，1.96；95%置信区间，1.34 - 2.86；p = 0.0003）。然而，两种基因型的联合效应与单独任何一种基因型的效应相同（各自独立且相同）。这些发现与体外实验一致，体外实验显示在低浓度下tau介导α-突触核蛋白原纤维形成（剂量阈值效应）。
