Interaction between polymorphisms in cell-cycle genes and environmental factors in regulating cholinesterase activity in people with exposure to omethoate.

Xiaoran Duan,Wu Yao,Sihua Wang,Tuanwei Wang,Wei Wang,Yongli Yang,Pengpeng Wang,Liuxin Cui,Xiaolei Feng

doi:10.1098/rsos.172357

Abstract

Cholinesterase activity (ChA), the effective biomarker for organophosphate pesticide exposure, is possibly affected by single nucleotide polymorphisms (SNPs) in cell-cycle-related genes. One hundred and eighty workers with long-term exposure to omethoate and 115 healthy controls were recruited to explore the gene–gene and gene–environment interactions. The acetylthiocholine and dithio-bis-(nitrobenzoic acid) method was used to detect the cholinesterase activities in whole blood, erythrocytes and plasma. Genetic polymorphisms were determined by the PCR-RFLP and direct PCR electrophoresis methods. Statistical results showed that the cholinesterase activities of whole blood, erythrocytes and plasma in the exposure group were significantly lower than those in the control group (p < 0.001), and erythrocyte cholinesterase activities were associated with gender, smoking and drinking in the exposure group (p < 0.05). Single-locus analyses showed that there is a statistically significant difference in the ChA among the genotypes CC, CA and AA of the p21 rs1801270 locus in the control group (p = 0.033), but not in the exposure group. A significant interaction between genes and environmental factors (i.e. p53, p21, mdm2, gender, smoking and drinking) affecting ChA was found through a generalized multifactor dimensionality reduction analysis. These obtained markers will be useful in further marker-assisted selection in workers with exposure to omethoate.

Highlights

Omethoate is a broad category of organophosphorous pesticides (OPs) with increasing domestic use, which has highly toxic and effective features [1]
Six polymorphic loci of p53 rs1042522, p53 rs17878362, p53 rs1625895, p21 rs1801270, p21 rs1059234 and mdm2 rs3730485 from the three genes were detected using genomic DNA isolated from peripheral blood lymphocytes
Acute poisoning incidents caused by OPs have been reduced, while the chronic toxic effect on human health caused by long-term, low-dose exposure to OPs has attracted people’s attention gradually [27,28]

Summary

Introduction

Omethoate is a broad category of organophosphorous pesticides (OPs) with increasing domestic use, which has highly toxic and effective features [1]. Genetic polymorphisms in cell-cycle-regulating genes may influence the DNA damage [8]. It has been shown that DNA damage could change the level of ChA through effects on the quantity and quality of red blood cells. The downstream gene of the p53 gene, p21, can prevent cell-cycle progression in the G1/S and G2/M phases and plays an important role in suppressing cancer [11]. The Mdm gene is a negative regulator of p53 which inhibits p53 expression [12]; and p53 could upregulate p21 expression in response to DNA-damaging agents [13]. No study has been found related to the correlations between the polymorphisms of p53, p21 and mdm genes and cholinesterase activities

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