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

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.

Interactions among variants in P53 apoptotic pathway genes are associated with neurologic deterioration and functional outcome after acute ischemic stroke

“…Up to date, there were no studies to investigate the association of interaction among the SNPs of P53 , P21 , MDM‐2 , and MMP‐9 with ND or functional outcome after IS. However, Duan et al (2018) has revealed that interaction among P53 , P21 , and MDM‐2 may affect cholinesterase activity in people with exposure to omethoate. Thus, we reason that the high‐risk interaction among P53 , MDM‐2 , and MMP‐9 could synergistically activate the intrinsic apoptotic pathway and ischemia‐induced apoptotic cell death, thereby increasing the risk of ND and poor functional outcome after IS.…”

“…The detailed information of the 9 SNPs in this study was summarized in Table 7. Extensive evidences have shown that SNPs of P53 and MDM2 rs2279744 play important roles in DNA damage and cell apoptosis and were independently related to high risk of cancer (Chen et al, 2015; Duan et al, 2018; Liu et al, 2011). Human P 53 Arg72Pro (rs1042522) SNP controls susceptibility to ischemia‐induced neuronal apoptosis and the functional outcome after stroke (Gomez‐Sanchez et al, 2011).…”

“…Rs1042522 polymorphism may affect neuronal vulnerability to apoptosis and can be considered as a genetic marker for poor functional outcome after stroke (Gomez-Sanchez et al, 2011). Many studies have shown that single nucleotide polymorphisms (SNPs) of P53, MDM-2, and P21 rs1801270 play important roles in DNA damage and apoptosis and are intimately related to cancer occurrence (Chen et al, 2015;Duan et al, 2018).…”

“…The detailed information of the 9 SNPs in this study was summarized in Table 7. Extensive evidences have shown that SNPs of P53 and MDM2 rs2279744 play important roles in DNA damage and cell apoptosis and were independently related to high risk of cancer (Chen et al, 2015;Duan et al, 2018;Liu et al, 2011). Human P53…”

“…Rs1042522 polymorphism may affect neuronal vulnerability to apoptosis and can be considered as a genetic marker for poor functional outcome after stroke (Gomez‐Sanchez et al, 2011). Many studies have shown that single nucleotide polymorphisms (SNPs) of P53 , MDM‐2 , and P21 rs1801270 play important roles in DNA damage and apoptosis and are intimately related to cancer occurrence (Chen et al, 2015; Duan et al, 2018). Matrix metalloproteinase‐9 (MMP‐9) can activate numerous pro‐inflammatory cytokines and chemokines such as interleukin and tumor necrosis factor, facilitates leukocytes transport across the endothelium, and plays a key role in neuronal damage, apoptosis, and blood–brain barrier (BBB) destruction after cerebral ischemia (Barr et al, 2010; Candelario‐Jalil, Yang, & Rosenberg, 2009).…”