Genetic polymorphisms and organophosphate neurotoxicity amongst emerging farmers in the Western Cape

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dc.contributor.advisorDalvie, Mohamed Aqielen_ZA
dc.contributor.advisorHoltman, Zeldaen_ZA
dc.contributor.advisorRamesar, Rajen_ZA
dc.contributor.authorGlass, Tracyen_ZA
dc.date.accessioned2017-01-23T07:39:27Z
dc.date.available2017-01-23T07:39:27Z
dc.date.issued2016en_ZA
dc.description.abstractBACKGROUND: Long-term exposure to organophosphates (OPs) can cause chronic neurotoxic effects which may be modulated by genetic polymorphisms of xenobiotic metabolising enzymes (XMEs). No previous study investigated XME modulation of neurotoxicity outcomes. OBJECTIVES: To investigate whether XMEs polymorphisms modulate OP neurotoxicity among emerging farmers. METHODS: A cross-sectional study of 301 emerging farmers was conducted in the rural Western Cape of South Africa. Neurotoxicity testing included the World Health Organisation Core Test Battery (digit span forward and backward) and vibration sensitivity testing. Questionnaire items included demographic data, potential confounders and work history of pesticide exposures. Blood samples were analysed for genetic polymorphisms of the following XMEs; glutathione S-transferases (GST), N-acetyltransferases (NAT) and Paraoxonase (PON1). RESULTS: Median age was 39 (30-48) and most had 9 years of education or less (65.5%). 54% of the participants were OP pesticide applicators. There was a low prevalence of the GST null genotype (GSTT-1% and GSTM-16%) and the GA and GG genotype for NAT (10%). Modulation of OP exposure and neurotoxic outcome relationships by NAT, PON1 at position 192 and GST was indicated in multivariate analysis. The strongest evidence of modification was by NAT on the relationship between pesticide poisoning and impaired vibration sense. Poisoned individuals with the GG genotype were more likely to suffer from impaired vibration sense compared to GA and AA genotypes. CONCLUSION: Genetic polymorphisms of NAT, PON1 (at position 192) and GSTM may modify the relationship between OP exposure and neurotoxicity. Larger longitudinal studies are required to determine whether preventive strategies can be developed to improve health amongst the identified vulnerable groups.en_ZA
dc.identifier.apacitationGlass, T. (2016). <i>Genetic polymorphisms and organophosphate neurotoxicity amongst emerging farmers in the Western Cape</i>. (Thesis). University of Cape Town ,Faculty of Health Sciences ,Centre for Infectious Disease Epidemiology and Research (CIDER). Retrieved from http://hdl.handle.net/11427/22873en_ZA
dc.identifier.chicagocitationGlass, Tracy. <i>"Genetic polymorphisms and organophosphate neurotoxicity amongst emerging farmers in the Western Cape."</i> Thesis., University of Cape Town ,Faculty of Health Sciences ,Centre for Infectious Disease Epidemiology and Research (CIDER), 2016. http://hdl.handle.net/11427/22873en_ZA
dc.identifier.citationGlass, T. 2016. Genetic polymorphisms and organophosphate neurotoxicity amongst emerging farmers in the Western Cape. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Glass, Tracy AB - BACKGROUND: Long-term exposure to organophosphates (OPs) can cause chronic neurotoxic effects which may be modulated by genetic polymorphisms of xenobiotic metabolising enzymes (XMEs). No previous study investigated XME modulation of neurotoxicity outcomes. OBJECTIVES: To investigate whether XMEs polymorphisms modulate OP neurotoxicity among emerging farmers. METHODS: A cross-sectional study of 301 emerging farmers was conducted in the rural Western Cape of South Africa. Neurotoxicity testing included the World Health Organisation Core Test Battery (digit span forward and backward) and vibration sensitivity testing. Questionnaire items included demographic data, potential confounders and work history of pesticide exposures. Blood samples were analysed for genetic polymorphisms of the following XMEs; glutathione S-transferases (GST), N-acetyltransferases (NAT) and Paraoxonase (PON1). RESULTS: Median age was 39 (30-48) and most had 9 years of education or less (65.5%). 54% of the participants were OP pesticide applicators. There was a low prevalence of the GST null genotype (GSTT-1% and GSTM-16%) and the GA and GG genotype for NAT (10%). Modulation of OP exposure and neurotoxic outcome relationships by NAT, PON1 at position 192 and GST was indicated in multivariate analysis. The strongest evidence of modification was by NAT on the relationship between pesticide poisoning and impaired vibration sense. Poisoned individuals with the GG genotype were more likely to suffer from impaired vibration sense compared to GA and AA genotypes. CONCLUSION: Genetic polymorphisms of NAT, PON1 (at position 192) and GSTM may modify the relationship between OP exposure and neurotoxicity. Larger longitudinal studies are required to determine whether preventive strategies can be developed to improve health amongst the identified vulnerable groups. DA - 2016 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2016 T1 - Genetic polymorphisms and organophosphate neurotoxicity amongst emerging farmers in the Western Cape TI - Genetic polymorphisms and organophosphate neurotoxicity amongst emerging farmers in the Western Cape UR - http://hdl.handle.net/11427/22873 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/22873
dc.identifier.vancouvercitationGlass T. Genetic polymorphisms and organophosphate neurotoxicity amongst emerging farmers in the Western Cape. [Thesis]. University of Cape Town ,Faculty of Health Sciences ,Centre for Infectious Disease Epidemiology and Research (CIDER), 2016 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/22873en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentCentre for Infectious Disease Epidemiology and Research (CIDER)en_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherEpidemiology and Biostatisticsen_ZA
dc.titleGenetic polymorphisms and organophosphate neurotoxicity amongst emerging farmers in the Western Capeen_ZA
dc.typeMaster Thesis
dc.type.qualificationlevelMasters
dc.type.qualificationnameMPHen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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