Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042961 (volvulus)
 4,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The potential for the development of ivermectin (IVM) resistance in microfilariae of Onchocerca volvulus and the existence of IVM tolerance in adult worms of this human pathogen are major concerns for the effective control of onchocerciasis. P-glycoprotein (P-gp), an ATP-binding transporter protein associated with multidrug resistance in mammals, protozoa and the nematode, Haemonchus contortus, might play important roles in the development of IVM resistance and/or in the tolerance of adult O. volvulus. In order to find the homologues of P-gp in O. volvulus, reverse transcription polymerase chain reaction (RT-PCR) has been performed in a specially synthesized cDNA pool and two full-length cDNAs have been cloned and sequenced. The first, ovpgp-1, encodes a 1278-amino-acid putative protein (OVPGP-1) with tandemly duplicated halves, each containing six putative transmembrane motifs and an ATP-binding cassette. OVPGP-1 is most similar in sequence to other eukaryotic P-gps. The second cDNA, ovplp-1, encodes a 587-amino-acid P-gp-like protein, which is only half the size of typical P-gps although it still shares high homology with them. Expression patterns of the two genes in different developmental stages have been investigated by semiquantitative RT PCR, suggesting that the expression levels of the two genes (especially ovpgp-1) may be linked with IVM sensitivity; low levels were found in IVM sensitive larval stages while high levels were found in IVM tolerant adult worms.
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PMID:Identification and stage-specific expression of two putative P-glycoprotein coding genes in Onchocerca volvulus. 1049 83

ATP-binding cassette (ABC) transporters comprise a large paralogous protein family and several confer drug resistance. Ivermectin (IVM) is the only drug approved for treatment of onchocerciasis and is a substrate for some ABC transporters. Furthermore, there is accumulating evidence that IVM selects on some ABC transporter genes in Onchocerca volvulus and other parasitic nematodes. The onchocerciasis control programs rely on community based treatment with IVM each year to reduce morbidity and decrease parasite transmission. This appears to be imposing selection pressure on O. volvulus. A half-size ABC transporter cDNA has previously been reported for O. volvulus, however, the full length gene has not been previously characterized and investigated for possible selection by IVM. Genes under selection may be identified by patterns of linkage disequilibrium (LD) and a loss of genetic polymorphism at physically linked loci. Twelve genetic markers spanning the full gene were examined in O. volvulus from non-treated and IVM treated populations in Ghana. Analysis of the genomic organization of the half-size ABC transporter (OvPLP) indicates that it spans approximately 3.8 kb comprising nine exons. Worms from treated people showed a reduction in gene diversity, a loss of genetic polymorphism at several markers, a selection for specific alleles, and a reduction in the number of regions in LD; these effects were more pronounced as treatment increased. These changes suggest that IVM is imposing selection pressure on this gene. The region between transmembrane domains four and five may be a useful marker for IVM selection in O. volvulus.
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PMID:Characterization of a half-size ATP-binding cassette transporter gene which may be a useful marker for ivermectin selection in Onchocerca volvulus. 1625 66