The patterns of mutation and amplification of Plasmodium falciparum pfcrt and pfmdr1 genes in Thailand during the year 1988 to 2003

Abstract

The study investigated the patterns of pfmdr1 and pfcrt genetic polymorphisms in Plasmodium falciaprum isolates collected from Thailand during the periods 1988-1993 (35 isolates), and 2003 (21 isolates). Pfcrt polymorphisms were almost universal for the mutations at codons K76T, A220S, Q271E, N326S, and R371I. All parasites displayed the chloroquine (CQ)-resistant phenotypes. This data suggested that pfcrt gene was sufficient to CQ resistance but did not mediate level of resistance. The prevalence [number of isolates (%)] of pfmdr1 polymorphisms at codons N86Y, Y184F, S1034C, N1042D and D1246Y were five (9%), 48 (86%), ten (18%), and 15 (27%), respectively. All isolates carried the wild-type nucleotide at position 1246. Results support the role of pfmdr1 in modulating susceptibilities of the P. falciparum to CQ, QN, and MQ. The frequencies of the S1034C and N1042D pfmdr1 polymorphisms and number of gene copy were significantly different in isolates collected during the two periods, with a trend of increasing prevalence of wild-type genotypes and number of gene copy from 1988 to 2003. The prominent pattern of pfmdr1 at codons 86/184/1034/1042/1246 was NFSND, with prevalence increasing from 40% to 95% during the 10-year period.