Genetic polymorphism of the β-tubulin gene of Onchocerca volvulus in ivermectin naïve patients from Cameroon, and its relationship with fertility of the worms

Observations of low response of patients infected with Onchocerca volvulus to ivermectin suggest that the parasite may be under a selection process toward potential resistance. To limit the extension of this phenomenon, it is crucial to characterize the genes of O. volvulus that are involved. For th...

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Published inParasitology Vol. 132; no. 2; pp. 255 - 262
Main Authors BOURGUINAT, C., PION, S. D. S., KAMGNO, J., GARDON, J., GARDON-WENDEL, N., DUKE, B. O. L., PRICHARD, R. K., BOUSSINESQ, M.
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Published Cambridge, UK Cambridge University Press 01.02.2006
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Abstract Observations of low response of patients infected with Onchocerca volvulus to ivermectin suggest that the parasite may be under a selection process toward potential resistance. To limit the extension of this phenomenon, it is crucial to characterize the genes of O. volvulus that are involved. For this, O. volvulus adult worms collected before the introduction of ivermectin in an onchocerciasis endemic area of central Cameroon were genotyped for β-tubulin. To derive a baseline to investigate the selective pressure of ivermectin, we analysed (1) the frequency distribution of the β-tubulin alleles, and (2) the relationship between the different β-tubulin related genotypes and the fertility status of the female worms. The frequency of allele b of the β-tubulin gene was very low, as it was observed in West Africa. We observed a deficit of heterozygous female worms leading to Hardy Weinberg disequilibrium, which might be explained by a shorter life-span of these worms compared to the homozygous worms. Unexpectedly, our results also show that the heterozygous female worms were much less fertile than the homozygotes: more than two thirds of the homozygotes were fertile, whereas only 37% of the heterozygotes were fertile. These results will be further considered when analysing post-treatment data.
AbstractList Observations of low response of patients infected with Onchocerca volvulus to ivermectin suggest that the parasite may be under a selection process toward potential resistance. To limit the extension of this phenomenon, it is crucial to characterize the genes of O. volvulus that are involved. For this, O. volvulus adult worms collected before the introduction of ivermectin in an onchocerciasis endemic area of central Cameroon were genotyped for beta-tubulin. To derive a baseline to investigate the selective pressure of ivermectin, we analysed (1) the frequency distribution of the beta-tubulin alleles, and (2) the relationship between the different beta-tubulin related genotypes and the fertility status of the female worms. The frequency of allele b of the beta-tubulin gene was very low, as it was observed in West Africa. We observed a deficit of heterozygous female worms leading to Hardy Weinberg disequilibrium, which might be explained by a shorter life-span of these worms compared to the homozygous worms. Unexpectedly, our results also show that the heterozygous female worms were much less fertile than the homozygotes: more than two thirds of the homozygotes were fertile, whereas only 37% of the heterozygotes were fertile. These results will be further considered when analysing post-treatment data.
Observations of low response of patients infected with Onchocerca volvulus to ivermectin suggest that the parasite may be under a selection process toward potential resistance. To limit the extension of this phenomenon, it is crucial to characterize the genes of O. volvulus that are involved. For this, O. volvulus adult worms collected before the introduction of ivermectin in an onchocerciasis endemic area of central Cameroon were genotyped for β-tubulin. To derive a baseline to investigate the selective pressure of ivermectin, we analysed (1) the frequency distribution of the β-tubulin alleles, and (2) the relationship between the different β-tubulin related genotypes and the fertility status of the female worms. The frequency of allele b of the β-tubulin gene was very low, as it was observed in West Africa. We observed a deficit of heterozygous female worms leading to Hardy Weinberg disequilibrium, which might be explained by a shorter life-span of these worms compared to the homozygous worms. Unexpectedly, our results also show that the heterozygous female worms were much less fertile than the homozygotes: more than two thirds of the homozygotes were fertile, whereas only 37% of the heterozygotes were fertile. These results will be further considered when analysing post-treatment data.
Author PION, S. D. S.
BOURGUINAT, C.
DUKE, B. O. L.
BOUSSINESQ, M.
GARDON, J.
GARDON-WENDEL, N.
KAMGNO, J.
PRICHARD, R. K.
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Keywords Onchocerca volvulus
Cameroon
genetic polymorphism
β-tubulin
fertility
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Snippet Observations of low response of patients infected with Onchocerca volvulus to ivermectin suggest that the parasite may be under a selection process toward...
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StartPage 255
SubjectTerms Adolescent
Adult
Aged
Animals
Antiparasitic Agents - therapeutic use
Cameroon
Child
Drug Resistance
Female
fertility
Fertility - genetics
Gene Frequency - genetics
genetic polymorphism
Genotype
Humans
Ivermectin - therapeutic use
Male
Middle Aged
Odds Ratio
Onchocerca volvulus
Onchocerca volvulus - genetics
Onchocerca volvulus - isolation & purification
Onchocerca volvulus - physiology
Onchocerciasis - drug therapy
Onchocerciasis - parasitology
Phenotype
Polymerase Chain Reaction - methods
Polymorphism, Genetic - genetics
Polymorphism, Genetic - physiology
Tubulin - genetics
β-tubulin
Title Genetic polymorphism of the β-tubulin gene of Onchocerca volvulus in ivermectin naïve patients from Cameroon, and its relationship with fertility of the worms
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