Genetic susceptibility to intermediate myasthenia syndrome following organophosphate insecticides poisoning

OBJECTIVE: To explore the association of gene polymorphism of organophosphate insecticides (OPs) metabolic enzymes with intermediate myasthenia syndrome (IMS) following acute OPs poisoning. METHODS: Thirty six of 147 acute OPs poisoning patients developed IMS one to four days after poisoning. Peripheral blood samples were collected from all the patients and whole blood cholinesterase (ChE) activity was determined by DTNB spectrometry. The genetic polymorphism of CYP2E1 (1091C-->T) and GSTP1 (313A-->G) were analyzed by polymerase chain reaction (PCR)-restrict fragment length polymorphism, CYP1A1 (4889A-->G), GSTM1 and GSTT1 by allele-specific PCR, and PON1 at 55 codon (55L-->M) by PCR-single strand conformation polymorphism. RESULTS: The whole blood ChE activity in IMS patients was not significantly different from non-IMS patients at admission (38.22 +/- 17.56)% and (42.49 +/- 16.23)%, respectively, P > 0.05, but recovered much slower in IMS patients than that in non-IMS patients. The frequencies of heterozygote and variant homozygote of PON1 at 55 codon, GSTM1 null, and both GSTM1 and GSTT1 null were higher in IMS patients than those in non-IMS patients (P < 0.05), with odds ratios and their 95% confident intervals of 2.48 (1.06 - 5.78), 11.23 (2.95- 42.76), 2.53 (1.14 - 5.61) and 2.68 (1.20 - 5.97), respectively. CONCLUSIONS: Patients of OPs and its mixture poisoning with genotype of variant allele at 55 codon of PON1, GSTM1 null and both GSTM1 and GSTT1 null probably had higher risk for IMS.