Effect of paraoxonase 1 192 Q/R polymorphism on paraoxonase and acetylcholinesterase enzyme activities in a Turkish population exposed to organophosphate

Abstract

Organophosphate (OP) compounds are the most commonly used pesticide groups and they are commercially used in the market for local and industrial purposes. Paraoxonase 1 (PON1) enzyme plays an important role in biotransformation of OP compounds, which shows toxic effects via inhibiting the acetylcholinesterase (AChE). The aim of this study was to determine the effects of PON1 gene polymorphism and its effects on PON and AChE enzyme activities in individuals who were exposed to organophosphorus insecticides due to occupational reasons, and to profile the probability of susceptibility to organophosphorus compounds. For this purpose, 54 individuals who were exposed to OPs and 54 healthy unrelated controls were studied. First, PON1 and AChE enzyme activities were measured. Second, PON1 192 Q/R polymorphism was determined by standard polymerase chain reaction-restriction fragment length polymorphism technique. When the PON1 192 Q/R polymorphism was compared with PON1 enzyme activities, statistically significant association was found in both OP-exposed and control groups (p < 0.05). PON1 192 R(+) (QR + RR genotypes) genotype carriers had higher PON1 activities than 192 R(-) (QQ) genotype carriers. On the other hand, results were statistically analyzed in terms of AChE enzyme activities and there were statistically significant differences only in the OP-exposed group (p < 0.05). The mean AChE concentration in the OP-exposed group was determined as 33.79 ± 6.84 U/g haemoglobin (Hb) for PON1 192 R(+) carriers and 30.37 ± 7.62 U/g Hb for PON1 192 R(+) carriers. As a conclusion, PON1 and AChE activities were increasing according to the genotypes found in individuals having been exposed to OPs at a chronic level; 192 R(+) > 192 R(-), respectively.

Investigation of Paraoxanase Enzyme Polymorphism in Patients with Alopecia Areata

“…The RR genotype was the least frequent genotype in both groups. In studies of Turkish population showed that, there were differences between the control and patient group with respect to frequencies of QR (12,14,15) and QQ genotypes (16)(17)(18) in spite of the least frequent genotype was RR in all groups.…”

Genetic polymorphisms as determinants of pesticide toxicity: Recent advances

“…Subjects with the PON1 192 R (+) genotype (QR + RR genotypes) showed a higher PON1 activity than the 192 R (-) (QQ) genotype. Then the activity of the AChE enzyme was investigated, showing a significant difference only in the group exposed to OP.Thus, the Authors conclude that the enzymatic activities of PON1 and AChE are different between exposed and not exposed, increasing in relation to the genotypic profile of the exposed subject [51]. Furthermore, a study carried out on placental villous samples showed that OPs are able to modulate the gene encoding the placental butyryl-cholinesterase (BChE), this up-regulation represent an adaptative response to environmental insults [66].…”

“…The susceptibility to exposure can be evaluated by studying the most common polymorphisms of cytochrome P450, of glutathione transferases (including GSTM1, GSTP1, GSTT1); of acetyltransferases (NAT2) and paraoxonases (mostly PON1), which are mainly involved in the metabolism of organophosphorus compounds [48]. In the last years, several Authors focused their attention on glutathione-s-transferases (GSTs) family and paraoxonase (PON1, PON2, and PON3) family and literature data are continually being updated in this field [[49], [50], [51], [52], [53], [54]].…”

Genetic profile for the detection of susceptibility to poisoning by exposure to pesticides

“…However, its activity is affected by different polymorphisms present in its gene, and PON1 activity is affected by different polymorphisms present in its gene. In fact, around 400 polymorphisms have been identified, of which only three are of clinical relevance: one in the promoter region (rs705379; -108C/T), and two in the coding region (rs854560, A>T, L55M; rs662, A>G Q192R) [31,34,40,44]. In the promoter region, there is a change at position 108 upstream, from showing a reduced enzyme activity due to lower expression of the PON1 gene [43].…”

“…The resulting 55M mutated variant expresses a lower concentration of the enzyme in the bloodstream, which also results in reduced enzyme activity. This variant is associated with the mutated allele of the 108T polymorphism in the promoter region [41,35,43,44]. In the rs662 polymorphism of the coding region, there is an amino acid change at position 192 from glutamine (CAA) to arginine (CGA), which results in a structural change in the enzyme that affects its activity, depending on the metabolized substrate (Fig.…”