The interplay between environmental and genetic factors in Parkinson's disease susceptibility: The evidence for pesticides

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by dopaminergic neuron loss in the substantia nigra. Several genetic and environmental factors have been implicated in the pathogenesis of PD. Single risk factors are likely to exert relatively minor effects, whereas their interaction may prove to be sufficient to cause PD. In the present review we summarize current knowledge from human genetic association studies regarding the interaction between gene polymorphisms and pesticide exposure in the risk of PD. A number of genetic association studies have investigated joint effects between genes and pesticides on PD risk. They have provided some evidence that genetic susceptibility either in metabolism, elimination and transport of pesticides or in the extent of mitochondrial dysfunction, oxidative stress and neuronal loss may predispose individuals to PD if they have been exposed to pesticides. These findings confirm the importance of considering pesticide–gene interactions in future studies in order to gain a better understanding of the pathogenic mechanisms of PD.

► Pesticides–genes interactions are likely to underlie the pathogenesis of PD.
► Separate study of pesticides or genetic factors may fail to detect interactions.
► Genes may influence metabolism, elimination and transport of pesticides.
► Pesticides–genes interplay may affect the extent of oxidative stress.
► Pesticides–genes interaction may influence neuronal function and survival.