Genetic variability in ABCB1, occupational pesticide exposure, and Parkinson’s disease

Abstract

Background Studies suggested that variants in the ABCB1 gene encoding P-glycoprotein, a xenobiotic transporter, may increase susceptibility to pesticide exposures linked to Parkinson’s Disease (PD) risk. Objectives To investigate the joint impact of two ABCB1 polymorphisms and pesticide exposures on PD risk. Methods In a population-based case control study, we genotyped ABCB1 gene variants at rs1045642 (c.3435C/T) and rs2032582 (c.2677G/T/A) and assessed occupational exposures to organochlorine (OC) and organophosphorus (OP) pesticides based on self-reported occupational use and record-based ambient workplace exposures for 282 PD cases and 514 controls of European ancestry. We identified active ingredients in self-reported occupational use pesticides from a California database and estimated ambient workplace exposures between 1974 and 1999 employing a geographic information system together with records for state pesticide and land use. With unconditional logistic regression, we estimated marginal and joint contributions for occupational pesticide exposures and ABCB1 variants in PD. Results For occupationally exposed carriers of homozygous ABCB1 variant genotypes, we estimated odds ratios of 1.89 [95% confidence interval (CI): (0.87, 4.07)] to 3.71 [95% CI: (1.96, 7.02)], with the highest odds ratios estimated for occupationally exposed carriers of homozygous ABCB1 variant genotypes at both SNPs; but we found no multiplicative scale interactions. Conclusions This study lends support to a previous report that commonly used pesticides, specifically OCs and OPs, and variant ABCB1 genotypes at two polymorphic sites jointly increase risk of PD.

Environment, lifestyle, and Parkinson's disease: Implications for prevention in the next decade

“…For example, paraquat exposure had limited association in persons with active glutathione‐S‐transferase T1, an enzyme involved in xenobiotic detoxification and glutathione metabolism, but was associated with an 11‐fold risk of PD in those with homozygous deletions of GSTT1 , a genotype that occurs in 20% of white and up to 40% of Asian populations. During the past decade, other examples of genes reported to interact with pesticide exposures include ABCB1 , which encodes the p‐glycoprotein transmembrane efflux pump, paraoxonase 1 , mitochondrial aldehyde dehydrogenase, and nitric oxide synthase . Virtually all of these studies used case‐control designs, and thus recall bias might result in greater exposure endorsement, but because persons are unaware of their genotypes, observations of gene–environment interaction are not likely the result of recall bias.…”

Of Pesticides and Men: a California Story of Genes and Environment in Parkinson’s Disease

“…Ambient work place and residential address derived OP and OC pesticide exposure as well as household or occupational OP or OC pesticide use increased PD risk as much as twofold in participants with one or less susceptibility alleles, but 3 to 4-fold in OP or OC exposed carriers of at least two susceptibility alleles (Table 2). [55]…”

Coffee consumption is associated with DNA methylation levels of human blood

“…We also related coffee consumption to DNAm levels in saliva samples from 127 PD patients and 129 PD-free controls (age-, gender-, and ethnicity-matched) enrolled in the second round of the PEG study (2009-ongoing). 18,19 Detailed information for each data set can be found in Supplementary Table S1 and in Methods section.…”