Plasmodium falciparum: linkage disequilibrium between loci in chromosomes 7 and 5 and chloroquine selective pressure in Northern Nigeria

Abstract

In view of the recent discovery (Molecular Cell6, 861–871) of a (Lys76Thr) codon change in genepfcrton chromosome 7 which determinesin vitrochloroquine resistance inPlasmodium falciparum, we have re-examined samples taken before treatment in our study in Zaria, Northern Nigeria (Parasitology119, 343–348). Drug resistance was present in 5/5 cases where thepfcrt76Thr codon change was seen (100% positive predictive value). Drug sensitivity was found in 26/28 cases where the change was absent (93% negative predictive value). Allelepfcrt76Thr showed strong linkage disequilibrium withpfmdr1Tyr86 on chromosome 5, more complete than that betweenpfcrtandcg2alleles situated between recombination cross-over points on chromosome 7. Physical linkage ofcg2withpfcrtmay account for linkage disequilibrium between their alleles but in the case of genespfmdr1andpfcrt, on different chromosomes, it is likely that this is maintained epistatically through the selective pressure of chloroquine.