Title |
Further evidence for the association of CYP2D6*4 gene polymorphism with Parkinson’s disease: a case control study
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Published in |
Genes and Environment, July 2017
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DOI | 10.1186/s41021-017-0078-8 |
Pubmed ID | |
Authors |
Anwarullah, Muhammad Aslam, Mazhar Badshah, Rashda Abbasi, Aneesa Sultan, Kafaitullah Khan, Nafees Ahmad, Jakob von Engelhardt |
Abstract |
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 CYP2D6 gene (CYP2D6*4 allele) is associated with PD because it alters the ability to metabolize toxins and in particular neurotoxins. CYP2D6 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 CYP2D6*4 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 CYP2D6*4 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. |
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