Simon David K, Wu Cai, Tilley Barbara C, Lohmann Katja, Klein Christine, Payami Haydeh, Wills Anne-Marie, Aminoff Michael J, Bainbridge Jacquelyn, Dewey Richard, Hauser Robert A, Schaake Susen, Schneider Jay S, Sharma Saloni, Singer Carlos, Tanner Caroline M, Truong Daniel, Wei Peng, Wong Pei Shieen, Yang Tianzhong
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
Department of Biostatistics, University of Texas Health Science Center School of Public Health at Houston, Houston, TX 77030, USA.
J Neurol Sci. 2017 Apr 15;375:355-359. doi: 10.1016/j.jns.2017.02.032. Epub 2017 Feb 17.
Caffeine is neuroprotective in animal models of Parkinson's disease (PD) and caffeine intake is inversely associated with the risk of PD. This association may be influenced by the genotype of GRIN2A, which encodes an NMDA-glutamate-receptor subunit. In two placebo-controlled studies, we detected no association of caffeine intake with the rate of clinical progression of PD, except among subjects taking creatine, for whom higher caffeine intake was associated with more rapid progression. We now have analyzed data from 420 subjects for whom DNA samples and caffeine intake data were available from a placebo-controlled study of creatine in PD. The GRIN2A genotype was not associated with the rate of clinical progression of PD in the placebo group. However, there was a 4-way interaction between GRIN2A genotype, caffeine, creatine and the time since baseline. Among subjects in the creatine group with high levels of caffeine intake, but not among those with low caffeine intake, the GRIN2A T allele was associated with more rapid progression (p=0.03). These data indicate that the deleterious interaction between caffeine and creatine with respect to rate of progression of PD is influenced by GRIN2A genotype. This example of a genetic factor interacting with environmental factors illustrates the complexity of gene-environment interactions in the progression of PD.
咖啡因在帕金森病（PD）动物模型中具有神经保护作用，且咖啡因摄入量与PD风险呈负相关。这种关联可能受GRIN2A基因型的影响，GRIN2A编码一种NMDA - 谷氨酸受体亚基。在两项安慰剂对照研究中，我们未发现咖啡因摄入量与PD临床进展速率之间存在关联，但在服用肌酸的受试者中除外，对这些受试者而言，较高的咖啡因摄入量与更快的进展相关。我们现在分析了来自420名受试者的数据，这些数据来自一项关于肌酸在PD中应用的安慰剂对照研究，其中有DNA样本和咖啡因摄入量数据。在安慰剂组中，GRIN2A基因型与PD临床进展速率无关。然而，GRIN2A基因型、咖啡因、肌酸和自基线以来的时间之间存在四向相互作用。在肌酸组中，咖啡因摄入量高的受试者中，而非咖啡因摄入量低的受试者中，GRIN2A T等位基因与更快的进展相关（p = ）。这些数据表明，咖啡因和肌酸在PD进展速率方面的有害相互作用受GRIN2A基因型影响。这个遗传因素与环境因素相互作用的例子说明了PD进展过程中基因 - 环境相互作用的复杂性。 （注：原文中“p=0.03”后面括号里内容缺失，译文按原文呈现）
