Chloroquine-resistance in Plasmodium falciparum is associated with polymorphisms in a locus on or near the cg2 gene on
chromosome 7, and in the pfmdr1 gene on chromosome 5. In this study we typed P. falciparum DNA from uncomplicated
malaria cases in The Gambia in 1990, 1995 and 1996 for size polymorphism in the omega repeat of cg2, for sequence
polymorphisms in pfmdr1 at codons 86 and 184, in dhfr at codon 108 and in the msp2 gene. Chloroquine sensitivity tests
were conducted in vitro. A significant but incomplete association was found between the presence of the cg2 Dd2-like
omega repeat size polymorphism and in vitro resistance, and between the tyr-86 allele of pfmdr1 and in vitro resistance.
Furthermore there was strong linkage disequilibrium between the pfmdr1 asn-86 allele and the cg2 not Dd2-like omega
repeat allele located on different chromosomes. In contrast, no linkage disequilibrium was found between these alleles and
either the dhfr ser-108 allele or the msp2 IC sequence polymorphism. No significant linkage was measured between pfmdr1
asn-86 and phe-184 although these loci are separated only by 296 base pairs. Our results suggest that genetic elements
linked to the cg2 and the pfmdr1 genes are important determinants of chloroquine resistance. It can be concluded that the
observed linkage disequilibrium is maintained epistatically through selection by chloroquine.