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 in | Parasitology Vol. 132; no. 2; pp. 255 - 262 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
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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. |
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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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Cites_doi | 10.1111/j.0014-3820.2000.tb00707.x 10.1016/S0001-706X(02)00117-1 10.1016/S0169-4758(00)01804-4 10.1179/000349804225003442 10.1016/S0140-6736(02)09456-4 10.1080/00034980120073184 10.1016/j.molbiopara.2005.01.021 10.1111/j.1558-5646.1999.tb05381.x 10.1016/S0304-4017(02)00321-7 10.1016/0035-9203(84)90264-5 10.1179/000349804225003415 10.1179/000349804225003253 10.1016/S0924-4204(99)80024-9 |
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References | Ardelli (S0031182005008899_ref003) 2005; 98 Via (S0031182005008899_ref019) 2000; 54 Remme (S0031182005008899_ref014) 1986; 64 Kläger (S0031182005008899_ref013) 1988; 39 Schulz-Key (S0031182005008899_ref016) 1977; 28 S0031182005008899_ref009 S0031182005008899_ref007 Vamosi (S0031182005008899_ref018) 1999; 53 S0031182005008899_ref008 Schulz-Key (S0031182005008899_ref015) 1988; 39 S0031182005008899_ref005 S0031182005008899_ref017 S0031182005008899_ref004 S0031182005008899_ref001 S0031182005008899_ref012 S0031182005008899_ref002 S0031182005008899_ref010 S0031182005008899_ref011 |
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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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