Mutations of transporter genes associated with drug resistance in Plasmodium Falciparum isolates from rural area of Sabah

• Main Authors: Khin Saw Naing, Shamsul Bahari Shamsudin
• Format: Research Report
• Language: English
• Published: Universiti Malaysia Sabah 2014
• Subjects: SF Animal culture
• Online Access: https://eprints.ums.edu.my/id/eprint/24833/1/Mutations%20of%20transporter%20genes%20associated%20with%20drug%20resistance%20in%20Plasmodium%20Falciparum%20isolates%20from%20rural%20area%20of%20Sabah.pdf; https://eprints.ums.edu.my/id/eprint/24833/

The successful use of chloroquine(CQ) through the decades finally resulted in CQ resistant(CQR) Plasmodium falciparum. These drug resistant parasites led to high fatality in humans. CQR P. falciparum strains were spread through the world from Colombia and Cambodia-Thailand border within these decades. The ATP-binding cassette (ABC) protein plays the major role in drug resistance in P. falciparum. Antimalarial drug resistance was associated with single nucleotide polymorphisms (SNPs) in genes encoding ABC proteins. Three genes which are well studied include pfcrt (Plasmodium falciparum CQ-resistance transporter) pfmdr 1 (Plasmodium falciparum multidrug resistance 1) and pfmrp 1 (Plasmodium falcipi!rum multidrug resistance protein 1) genes. All pfcrt alleles in CQR parasites consistently include mutations for K76T and A220S accompanied by changes in two to six other mutations. Pfcrt K76T SNP is the major molecular determinant of CQR P. falciparum strains. N86Y marker of pfmdr 1 gene and K76T marker of pfcrtgene were prevalent in CQR isolates. Another SNP which is well studied and highly prevalent in pfmdr 1 gene is Y184F. Five SNPs, two SNPs and 1 SNP in pfcrt, pfmdr 1 and pfmrp 1 genes respectively were studied by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and PCR-DNA sequencing methods in the current study. SVMNT and CVIET haplotypes of pfcrt gene were circulating in rural areas of Sabah. The results indicate that the drug resistant markers in drug resistant P. falciparum isolates from rural Sabah were supposed to be pfcrt 76T, 220S and pfmdr 1 84Y. Finally, we have succeeded to identify the molecular markers for CQR Plasmodlum falclparum for the rural areas of Sabah.