Publication: Variation in intronic microsatellites and exon 2 of the Plasmodium falciparum chloroquine resistance transporter gene during modification of artemisinin combination therapy in Thailand
0
0
Issued Date
2018
Resource Type
Language
eng
File Type
application/pdf
Access Rights
open access
Rights
ผลงานนี้เผยแพร่ภายใต้ สัญญาอนุญาตครีเอทีฟคอมมอนส์แบบ แสดงที่มา-ไม่ใช้เพื่อการค้า-ไม่ดัดแปลง 4.0 (CC BY-NC-ND 4.0)
Rights Holder(s)
มหาวิทยาลัยศรีนครินทรวิโรฒ
Bibliographic Citation
Infection, Genetics and Evolution
Volume 65, November 2018, Pages 35-42
Suggested Citation
Sunee Seethamchai, Buppan, P, Kuamsab, N., Teeranaipong, P., Putaporntip, C, Jongwutiwes, S Variation in intronic microsatellites and exon 2 of the Plasmodium falciparum chloroquine resistance transporter gene during modification of artemisinin combination therapy in Thailand. Infection, Genetics and Evolution
Volume 65, November 2018, Pages 35-42. doi:https://doi.org/10.1016/j.meegid.2018.07.015 Retrieved from: https://hdl.handle.net/20.500.14740/11840
Organization
Abstract
The amino acid substitution at residue 76 of the food vacuolar transmembrane protein encoded by the chloroquine resistance transporter gene of Plasmodium falciparum (Pfcrt) is an important, albeit imperfect, determinant of chloroquine susceptibility status of the parasite. Other mutations in Pfcrt can modulate susceptibility of P. falciparum to other antimalarials capable of interfering with heme detoxification process, and may exert compensatory effect on parasite growth rate. To address whether nationwide implementation of artemisinin combination therapy (ACT) in Thailand could affect sequence variation in exon 2 and introns of Pfcrt, we analyzed 136 P. falciparum isolates collected during 1997 and 2016 from endemic areas bordering Myanmar, Cambodia and Malaysia. Results revealed 6 haplotypes in exon 2 of Pfcrt with 2 novel substitutions at c.243A > G (p.R81) and c.251A > T (p.N84I). Positive selection was observed at amino acid residues 75, 76 and 97. Four, 3, and 2 alleles of microsatellite (AT/TA) repeats occurred in introns 1, 2 and 4, respectively, resulting in 7 different 3-locus haplotypes. The number of haplotypes and haplotype diversity of exon 2, and introns 1, 2 and 4 were significantly greater among isolates collected during 2009 and 2016 than those collected during 1997 and 2008 when 3-day ACT and 2-day ACT regimens were implemented nationwide, respectively (p < 0.05). By contrast, the number of haplotypes and haplotype diversity of the merozoite surface proteins 1 and 2 of these parasite populations did not differ significantly between these periods. Therefore, the Pfcrt locus of P. falciparum in Thailand continues to evolve and could have been affected by selective pressure from modification of ACT regimen.