K-variant BCHE and pesticide exposure: Gene-environment interactions in a case\u2013control study of Parkinson\u2019s disease in Egypt

Thomas W Rösler,Samia Ashour,Mohamed Moharram,Gregor Kuhlenbäumer,Ali S Shalash,Ulrich Müller,Astrid Dempfle,Ehab El-Seidy,Mohammad El-Kattan,Gharib Fawi,Amal El-Motayam,Mohamed El-Gamal,Muhammad Abdel-Naby,Abdelhalim El-Tantawy,Mohamed El-Sherif,Mohamed Salama,Günter U Höglinger,Eman M Khedr

doi:10.1038/s41598-018-35003-4

Abstract

Pesticide exposure is associated with increased risk of Parkinson’s disease (PD). We investigated in Egypt whether common variants in genes involved in pesticide detoxification or transport might modify the risk of PD evoked by pesticide exposure. We recruited 416 PD patients and 445 controls. Information on environmental factors was collected by questionnaire-based structured interviews. Candidate single-nucleotide polymorphisms (SNPs) in 15 pesticide-related genes were genotyped. We analyzed the influence of environmental factors and SNPs as well as the interaction of pesticide exposure and SNPs on the risk of PD. The risk of PD was reduced by coffee consumption [OR = 0.63, 95% CI: 0.43–0.90, P = 0.013] and increased by pesticide exposure [OR = 7.09, 95% CI: 1.12–44.01, P = 0.036]. The SNP rs1126680 in the butyrylcholinesterase gene BCHE reduced the risk of PD irrespective of pesticide exposure [OR = 0.38, 95% CI: 0.20–0.70, P = 0.002]. The SNP rs1803274, defining K-variant BCHE, interacted significantly with pesticide exposure (P = 0.007) and increased the risk of PD only in pesticide-exposed individuals [OR = 2.49, 95% CI: 1.50–4.19, P = 0.0005]. The K-variant BCHE reduces serum activity of butyrylcholinesterase, a known bioscavenger for pesticides. Individuals with K-variant BCHE appear to have an increased risk for PD when exposed to pesticides.

Highlights

Pesticide exposure is associated with increased risk of Parkinson’s disease (PD)
The study sample consisted of n = 416 unrelated PD patients and n = 445 unrelated healthy controls of Egyptian ancestry (Table 1)
The sex distribution did not differ between the groups, but PD patients were older than controls

Summary

Introduction

Pesticide exposure is associated with increased risk of Parkinson’s disease (PD). The SNP rs1126680 in the butyrylcholinesterase gene BCHE reduced the risk of PD irrespective of pesticide exposure [OR = 0.38, 95% CI: 0.20–0.70, P = 0.002]. The SNP rs1803274, defining K-variant BCHE, interacted significantly with pesticide exposure (P = 0.007) and increased the risk of PD only in pesticide-exposed individuals [OR = 2.49, 95% CI: 1.50–4.19, P = 0.0005]. Three meta-analyses of epidemiological studies investigating the association of pesticides and PD have been carried out so far[5,6] They consistently concluded that pesticide exposure and factors related to pesticide exposure (e.g. rural living, farming or well water drinking) are positively associated with the risk to develop PD5,6

Methods

Results

Conclusion