Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Resistance to the insecticide DDT in the mosquito vectors of malaria has severely hampered efforts to control this disease and has contributed to the increase in prevalence of malaria cases seen in recent years. Over 90% of the 300-500 million annual cases of malaria occur in Africa, where the major vector is Anopheles gambiae. DDT resistance in the ZAN/U strain of An. gambiae is associated with an increased metabolism of the insecticide, catalysed by members of the glutathione S-transferase (GST) enzyme family, but the molecular mechanism underlying this metabolic resistance is not known. Genetic crosses show that resistance is autosomal and semidominant. We have used microsatellite markers to identify two quantitative trait loci (QTL), which together explain over 50% of the variance in susceptibility to DDT in the ZAN/U strain of An. gambiae. The first locus, rtd1, is on chromosome 3 between markers H341 and H88 and has a recessive effect with respect to susceptibility. The second locus, rtd2 is on chromosome 2L, close to marker H325 and has an additive genetic effect. The markers flanking these two QTL have been physically mapped to An. gambiae polytene chromosomes. They do not coincide with any of the GST genes that have been cloned and mapped in this species. Characterization of these QTL will lead to a clearer understanding of the mechanisms of metabolic resistance to DDT.
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PMID:Genetic mapping of two loci affecting DDT resistance in the malaria vector Anopheles gambiae. 1102 68

Metabolic pathways play an important role in insecticide resistance, but the full spectra of the genes involved in resistance has not been established. We constructed a microarray containing unique fragments from 230 Anopheles gambiae genes putatively involved in insecticide metabolism [cytochrome P450s (P450s), GSTs, and carboxylesterases and redox genes, partners of the P450 oxidative metabolic complex, and various controls]. We used this detox chip to monitor the expression of the detoxifying genes in insecticide resistant and susceptible An. gambiae laboratory strains. Five genes were strongly up-regulated in the dichlorodiphenyltrichloroethane-resistant strain ZAN/U. These genes included the GST GSTE2, which has previously been implicated in dichlorodiphenyltrichloroethane resistance, two P450s, and two peroxidase genes. GSTE2 was also elevated in the pyrethroid-resistant RSP strain. In addition, the P450 CYP325A3, belonging to a class not previously associated with insecticide resistance, was expressed at statistically higher levels in this strain. The applications of this detox chip and its potential contribution to malaria vector insecticide resistance management programs are discussed.
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PMID:The Anopheles gambiae detoxification chip: a highly specific microarray to study metabolic-based insecticide resistance in malaria vectors. 1575 17