Aslam Muhammad, Badshah Mazhar, Abbasi Rashda, Sultan Aneesa, Khan Kafaitullah, Ahmad Nafees, von Engelhardt Jakob
Synaptic Signalling and Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Department of Biochemistry, Quaid-i-Azam University, Islamabad, Pakistan.
Genes Environ. 2017 Jul 1;39:18. doi: 10.1186/s41021-017-0078-8. eCollection 2017.
Genetic and environmental risk factors play an important role for the susceptibility to sporadic Parkinson's disease (PD). It was hypothesized that a splice variant of the gene ( allele) is associated with PD because it alters the ability to metabolize toxins and in particular neurotoxins. codes for the drug metabolizing enzyme debrisoquine 4-hydroxylase. The CYP2D6*4 variant results in an undetectable enzyme activity and consequently in a reduction in metabolism of some toxins.
Some of agricultural chemicals have neurotoxic potential and CYP2D6 is involved in their detoxification. Thus, we conducted a case control study to investigate the association of the CYP2D6*4 with PD in a Pakistani subpopulation that is known to be exposed to high levels of some agricultural pesticides, insecticides and herbicides.
We found a significantly higher allele and genotype frequency of the variant in 174 sporadic PD patients when compared to 200 controls. In addition, there was a trend to an earlier age of PD onset and a tremor dominant phenotype in variant carriers.
Our data provide further evidence that a poor metabolizer status may increase the risk to develop PD especially in populations that are exposed to environmental toxins.
遗传和环境风险因素在散发性帕金森病（PD）的易感性中起重要作用。据推测，某基因的一种剪接变体（等位基因）与PD相关，因为它改变了代谢毒素尤其是神经毒素的能力。该基因编码药物代谢酶去甲异喹胍4-羟化酶。CYP2D6*4变体导致无法检测到酶活性，从而导致某些毒素的代谢减少。
一些农用化学品具有神经毒性潜力，且CYP2D6参与其解毒过程。因此，我们进行了一项病例对照研究，以调查在已知接触高水平某些农用杀虫剂、杀虫剂和除草剂的巴基斯坦亚人群中CYP2D6*4与PD的关联。
与200名对照相比，我们发现174例散发性PD患者中该变体的等位基因和基因型频率显著更高。此外，该变体携带者有PD发病年龄较早和震颤为主表型的趋势。
我们的数据提供了进一步的证据，表明代谢不良状态可能增加患PD的风险，尤其是在接触环境毒素的人群中。
