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

Abstract

Purpose 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.

Pesticides Exposure and Thyroid Hormone Levels Among Agricultural Workers and Pesticide Applicators: A Systematic Review

“…The geometric mean of FT 4 serum levels among groups exposed to only insecticide application was slightly higher compared to the unexposed (36,38). These results were similar to that of the groups exposed to various pesticide types (39,43,47,51) as demonstrated in Table 1.…”

“…Ten of eleven studies conducted with either farmers or farmworkers showed that exposure to various types of pesticides application significantly affected the level of thyroid hormone compared to unexposed groups (38)(39)(40)(41)(42)(43)(44)(45)(46)(47). However, the remaining one indicated that the difference in thyroid hormone levels among both exposed and unexposed groups was statistically insignificant (37) as presented in Table 1.…”

“…According to Table 1, 11 articles evaluated pesticide exposure among male farmers or farmworkers (37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47) and six studies were conducted with either pesticide applicators or sprayers (36,(48)(49)(50)(51). Fifteen studies measured serum levels of thyroid hormones including Thyroid Stimulating Hormone (TSH), Free Triiodothyronine (FT 3 ), Free Thyroxine (FT 4 ), Triiodothyronine (T 3 ), Thyroxine (T 4 ), and Total Triiodothyronine (T 3 ).…”

“…FT 3 serum levels were also investigated by five articles among either farmworkers or pesticide applicators exposed to various pesticide types (44)(45)(46)(47)51). Furthermore, three showed that FT 3 serum levels among exposed groups were significantly higher than in the unexposed (44,(46)(47). In contrast, the remaining two indicated that FT 3 serum levels were not different between both groups (45,51).…”

“…Thyroid hormone concentrations may change due to the effects of some pesticide types such as insecticides, herbicides, and/or fungicides on the hypothalamus-pituitary-thyroid axis. This involves disrupting central regulation, iodine uptake, thyroid hormone synthesis, and the hormone receptors' production ability (47).…”