Objectives: 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. Methods: 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. Results: 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 CYP2B6*1/*1 than among those with *1/*6 or *6/*6 genotypes. CYP2B6*6 gene polymorphisms, smoking, CEL, body mass index, and spraying time were retained in the final linear regression model as determinants of TCPy. Conclusions The results suggest that CYP2B6*6 gene polymorphisms may play an important role in influencing susceptibility to CPF exposure. CYP2B6*6 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.

Background and Objective: Premature ventricular complex (PVC) burden exhibits one of three circadian types, classified as fast-type, slow-type, and independent-type PVC. It is unknown whether PVC circadian types have different heart rate variability (HRV) parameter values. Therefore, this study aimed to evaluate differences in HRV circadian rhythm among fast-, slow-, and independent-type PVC. Methods: This cross-sectional observational study consecutively recruited 65 idiopathic PVC subjects (23 fast-, 20 slow-, and 22 independent-type) as well as five control subjects. Each subject underwent a 24-hour Holter to examine PVC burden and HRV. HRV analysis included components that primarily reflect global, parasympathetic, and sympathetic activities. Repeated measures analysis of variance was used to compare differences in HRV circadian rhythm by PVC type. Results. The average PVC burden was 15.7%, 8.4%, and 13.6% in fast-, slow-, and independent-type idiopathic PVC subjects, respectively. Global, parasympathetic nervous system, and sympathetic nervous system HRV parameters were significantly lower in independenttype PVC versus fast- and slow-type PVC throughout the day and night. Furthermore, we unexpectedly found that tendency towards sympathetic activity dominance during nighttime was only in independent-type PVC. Conclusion The HRV parameters are reduced in patients with independent-type PVC compared to fast- and slowtype PVC. Future research is warranted to determine possible differences in the prognosis between the three PVC types.
Ventricular Premature Complexes ; Circadian Rhythm ; Autonomic Nervous System

Objective: The objective of our study was to determine the genotype frequencies of CYP2C19*2 and *3 gene polymorphisms among Javanese farmers exposed to chlorpyrifos (CPF) in Central Java, Indonesia. Methods: This cross-sectional study was conducted from July to October 2020 in Central Java, Indonesia, involving 151 vegetable farmers aged 18-65 years who used CPF for at least one year. CYP2C19*2 and *3 gene polymorphisms were analyzed using PCR-RFLP. Direct calculations were applied to calculate allele and genotype frequencies. The difference in genotype frequencies among the sex and cumulative exposure level (CEL) group was performed using the Chi-square test. In contrast, the proportion difference of allele frequencies was analyzed using Z-test. Results: The frequency of CYP2C19 genotypes *1/*1, *1/*3, *1/*2, and *2/*2 were 64 %, 7 %, 23 % and 6 %. We observed no significant difference in the genotype distribution according to sex group and CEL group. Conclusion In summary, the prevalence of toxicologically relevant CYP2C19 polymorphisms was determined in the Javanese agricultural population. The CYP2C19 genotype may be helpful as an essential biomarker of genetic susceptibility towards CPF exposure. Nevertheless, further studies to confirm the role of CYP2C19 in this context are still needed.
Cytochrome P-450 CYP2C19 ; Pesticides