Abstract:
The human malaria parasite Plasmodium falciparum has been demonstrated to activate ClC-2 Cl- channels of the host erythrocyte. The activated channels contribute to the host cell volume homeostasis. From a population living in a malaria-endemic area (Gabon), all 24 Clcn2 exons were sequenced to evaluate the possible role of the Clcn2 gene in malaria. Six amino acid exchanges in the intracellular N-terminus (P48R, R68H), in a putative extracellular loop (G199A), or in the intracellular C-terminus (R646Q, R725W, R747H) were identified in low frequency in the Africans but not at all in a Caucasian control group. Heterologous expression of these polymorphisms in Xenopus laevis oocytes demonstrated their functional significance as determined by two-electrode voltage-clamp. In conclusion, the Africans' gene pool comprises Clcn2 polymorphisms that may affect ClC-2 channel function. The low prevalence of the functional amino acid exchanges precludes, however, safe conclusions as to their impact on the course of malaria.