Genetic Polymorphisms of Pesticide-Metabolizing Enzymes and Transporters in Agricultural Workers and Thyroid Hormone Levels

Abstract

Jintana Sirivarasai,1 Suwanee Chanprasertyothin,2 Pornpimol Kongtip,3 Susan Woskie4 1Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 2Research and Innovation Center, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 3Department of Occupational Health and Safety, Faculty of Public Health, Mahidol University, Bangkok, Thailand; 4Department of Public Health, University of Massachusetts Lowell, Lowell, MA, USACorrespondence: Jintana SirivarasaiFaculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama 6 Road, Ratchatavee District, Bangkok, 10400, ThailandTel [phone]Fax [phone]Email [email protected]: Chronic exposure to pesticides has been associated with thyroid dysfunction owing to their endocrine disruption ability. Genetic variations in genes encoding phase I and II enzymes and phase III transporters are partly responsible for individual responses to chemical pesticides. This study investigated the association between variations in genes involved in pesticide metabolism and altered thyroid hormone concentrations.Methods: We assessed thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) in organic agriculture workers (n = 216) and workers who used chemical pesticides (n = 229). A questionnaire was used to collect sociodemographic, pesticide exposure, and health status data. Blood samples were analyzed for TSH, FT3, and FT4. Genomic DNA was extracted and genotyped using the TaqMan real-time PCR genotyping assay and restriction fragment length polymorphism method for 15 metabolically related genes.Results: Significant differences in the TSH (1.58 vs 1.12 μIU/mL) and FT3 (0.34 vs 0.31 ng/dL) concentrations between the chemical and organic worker groups were observed. The frequencies of all single nucleotide polymorphisms were in Hardy–Weinberg equilibrium and were mostly consistent with Asian populations. The findings showed the association between SNPs of enzymes and transporters and TSH, FT3, and FT4. The odd ratio and adjusted odd ratio (with sex, age, smoking status, alcohol consumption and exposure parameters) for subclinical thyroid disease by the variant alleles CYP1A1 rs1048943, CYP2B6 rs2279343, CYP2C19 rs4244285, NAT2 rs1799931, and PON1 rs662 in the chemical workers compared with the organic workers were found (P values < 0.05).Conclusion: This is the first study to assess gene–environment interactions in Thai agricultural workers by investigating disruptions of the hypothalamic–pituitary–thyroid axis. The investigated SNP profiles revealed several gene–thyroid hormone associations in which even low levels of pesticide exposure could disturb thyroid homeostasis. These findings provide a foundation for planning future studies investigating associations between complex diseases and occupational pesticide exposure.Keywords: occupational pesticide exposure, enzyme phase I and II, transporters, genotype, thyroid-stimulating hormone

Keywords

• occupational pesticide exposure
• enzyme phase i and ii
• transporters
• genotype
• thyroid-stimulating hormone