Golbe Lawrence I, Di Iorio Giuseppe, Markopoulou Katerina, Athanassiadou Aglaia, Papapetropoulos Spiridon, Watts Ray L, Vance Jeffery M, Bonifati Vincenzo, Williams Tanishia A, Spychala John R, Stenroos E Scot, Johnson Williams G
Department of Neurology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.
Am J Med Genet B Neuropsychiatr Genet. 2007 Mar 5;144B(2):254-8. doi: 10.1002/ajmg.b.30450.
Monogenic forms of Parkinson's disease (PD) provide an opportunity to examine mechanisms underlying phenotypic variation. Glutathione S-transferase (GST) has detoxification and antioxidative functions. To screen genetic variations in GST for an effect on the onset age (OA) of PD, we typed seven common genetic polymorphisms in five GST isoenzymes, M1, M3, P1, T1, and Z1, in 36 affected individuals of Italian or Greek origin with the alpha-synuclein A53T (PARK1) mutation. Mean OA was 45.2 years with a wide SD of 11.03 years, similar to that of idiopathic PD. Our allelic analysis showed that the subjects homozygous for the GSTP1 G-for-A nucleotide substitution at position 313 had a mean OA acceleration of 15.2 years (31.3 +/- 7.09 years, n = 3 vs. 46.5 +/- 10.50 years, n = 33, P = 0.020). The GSTP1 C341T substitution was associated with a 9.7-year acceleration of OA, but the significance was borderline (36.4 +/- 8.35 years vs. 46.7 +/- 10.85 years, P = 0.0519). After correction for the five genes examined, both results lose statistical significance. Nevertheless, our results suggest that further investigation in GSTP1 variants and PD pathogenesis is warranted in sporadic PD and that a search for toxins that accelerate PD OA should pay particular attention to GST-P1 substrates.
帕金森病（PD）的单基因形式为研究表型变异背后的机制提供了契机。谷胱甘肽S-转移酶（GST）具有解毒和抗氧化功能。为了筛查GST基因变异对PD发病年龄（OA）的影响，我们对36名具有意大利或希腊血统且携带α-突触核蛋白A53T（PARK1）突变的患病个体，检测了5种GST同工酶（M1、M3、P1、T1和Z1）中的7种常见基因多态性。平均OA为45.2岁，标准差为11.03岁，与特发性PD相似。我们的等位基因分析显示，在313位核苷酸处GSTP1的G被A取代的纯合子受试者，平均OA加速了15.2岁（31.3±7.09岁，n = 3，对比46.5±10.50岁，n = 33，P = 0.020）。GSTP1 C341T取代与OA加速9.7岁相关，但显著性接近临界值（36.4±8.35岁对比46.7±10.85岁，P = 0.0519）。在对所检测的5个基因进行校正后，两个结果均失去统计学意义。尽管如此，我们的结果表明，对于散发性PD，有必要进一步研究GSTP1变异与PD发病机制，并且在寻找加速PD OA的毒素时，应特别关注GST-P1底物。
