Abstract
Polymorphisms in genes encoding xenobiotic-metabolizing enzymes (XME) are important parameters accounting for the wide inter-individual variability to environmental exposures. Paraoxonase-1 (PON1), butyrylcholinesterase (BChE) and Cytochrome-P450 constitute major classes of XME involved in the detoxification of pesticide chemicals, in particular organophosphates. This study explored the allelic frequency, linkage disequilibrium and haplotype analysis of ten common polymorphic variants of seven key genes involved in organophosphate metabolism (BCHE-K, BCHE-A, PON1 Q192R, PON1 L55M, PON1 -108C/T, CYP2C19 G681A, CYP2D6 G1846A, CYP3AP1 -44G/A, GSTM1∗0 and GSTT1∗0) in a children population living near an intensive agriculture area in Spain. It was hypothesized that individuals with unfavorable combinations of gene variants will be more susceptible to adverse effects from organophosphate exposure. Genomic DNA from 496 healthy children was isolated and amplified by PCR. Hydrolysis probes were used for the detection of eight specific SNPs and two copy number variants (CNVs) by using TaqMan® Assay-based real-time PCR. Frequencies of SNPs and CNVs in the target genes were in Hardy-Weinberg equilibrium and broadly consistent with European...Continue Reading
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