Genetic polymorphism of the beta-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 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.
Bourguinat
C
C
Institute of Parasitology, McGill University, Sainte Anne-de-Bellevue, Quebec, Canada H9X3V9.
Pion
S D S
SD
Kamgno
J
J
Gardon
J
J
Gardon-Wendel
N
N
Duke
B O L
BO
Prichard
R K
RK
Boussinesq
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000977:Antiparasitic Agents / Q000627:therapeutic use; D002163:Cameroon; D002648:Child; D004351:Drug Resistance; D005260:Female; D005298:Fertility / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D007559:Ivermectin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D017181:Onchocerca volvulus / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D009855:Onchocerciasis / Q000188:drug therapy / Q000469:parasitology*; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic / Q000235:genetics / Q000502:physiology*; D014404:Tubulin / Q000235:genetics*
D000977:Antiparasitic Agents; D014404:Tubulin; D007559:Ivermectin