Doctoral Program, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia.
Department of Occupational Health and Safety, Faculty of Medicine and Health Science Universitas Kristen Krida Wacana, Jakarta, Indonesia.
J Prev Med Public Health. 2022 May;55(3):280-288. doi: 10.3961/jpmph.21.641. Epub 2022 May 16.
One of the most widely used pesticides today is chlorpyrifos (CPF). Cytochrome P450 (CYP)2B6, the most prominent catalyst in CPF bioactivation, is highly polymorphic. The objective of our study was to evaluate the role of CYP2B6*6, which contains both 516G>T and 785A>G polymorphisms, in CPF toxicity, as represented by the concentration of 3,5,6-trichloro-2-pyridinol (TCPy), among vegetable farmers in Central Java, Indonesia, where CPF has been commonly used.
A cross-sectional study was conducted among 132 vegetable farmers. Individual socio-demographic and occupational characteristics, as determinants of TCPy levels, were obtained using a structured interviewer-administered questionnaire and subsequently used to estimate the cumulative exposure level (CEL). TCPy levels were detected with liquid chromatography-mass spectrometry. CYP2B6*6 gene polymorphisms were analyzed using a TaqMan® SNP Genotyping Assay and Sanger sequencing. Linear regression analysis was performed to analyze the association between TCPy, as a biomarker of CPF exposure, and its determinants.
The prevalence of CYP2B6*6 polymorphisms was 31% for *1/*1, 51% for *1/*6, and 18% for *6/6. TCPy concentrations were higher among participants with CYP2B61/*1 than among those with *1/*6 or *6/6 genotypes. CYP2B66 gene polymorphisms, smoking, CEL, body mass index, and spraying time were retained in the final linear regression model as determinants of TCPy.
The results suggest that CYP2B66 gene polymorphisms may play an important role in influencing susceptibility to CPF exposure. CYP2B66 gene polymorphisms together with CEL, smoking habits, body mass index, and spraying time were the determinants of urinary TCPy concentrations, as a biomarker of CPF toxicity.
目前使用最广泛的农药之一是毒死蜱（CPF）。细胞色素 P450（CYP）2B6 是 CPF 生物活化的最主要的催化剂，其具有高度多态性。本研究的目的是评估 CYP2B66 在 CPF 毒性中的作用，CYP2B66 包含 516G>T 和 785A>G 两种多态性，其代表物是 3,5,6-三氯-2-吡啶醇（TCPy），研究对象是印度尼西亚中爪哇的蔬菜种植者，那里广泛使用 CPF。
我们进行了一项横断面研究，共纳入 132 名蔬菜种植者。使用结构化访谈问卷调查了个体社会人口学和职业特征，作为 TCPy 水平的决定因素，并随后用于估计累积暴露水平（CEL）。使用液相色谱-质谱法检测 TCPy 水平。使用 TaqMan® SNP 基因分型检测和 Sanger 测序分析 CYP2B6*6 基因多态性。采用线性回归分析方法分析 TCPy（CPF 暴露的生物标志物）与各决定因素之间的关系。
CYP2B66 多态性的流行率分别为1/*1 为 31%，*1/*6 为 51%，*6/6 为 18%。与 CYP2B61/1 基因型相比，携带1/6 或6/6 基因型的参与者 TCPy 浓度更高。CYP2B66 基因多态性、吸烟、CEL、体重指数和施药时间保留在最终的线性回归模型中，作为 TCPy 的决定因素。
结果表明，CYP2B66 基因多态性可能在影响 CPF 暴露易感性方面发挥重要作用。CYP2B66 基因多态性与 CEL、吸烟习惯、体重指数和施药时间共同决定了尿 TCPy 浓度，作为 CPF 毒性的生物标志物。
