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Original Article

Plasmodium vivax Drug Resistance Genes; Pvmdr1 and Pvcrt-o Polymorphisms in Relation to Chloroquine Sensitivity from a Malaria Endemic Area of Thailand

Kanchana Rungsihirunrat1, Poonuch Muhamad2, Wanna Chaijaroenkul3, Jiraporn Kuesap4, Kesara Na-Bangchang3,*
The Korean Journal of Parasitology 2015;53(1):43-49.
Published online: February 27, 2015

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*Corresponding author (kesaratmu@yahoo.com)
• Received: June 7, 2014   • Revised: November 16, 2014   • Accepted: December 3, 2014

© 2015, Korean Society for Parasitology and Tropical Medicine

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Plasmodium vivax Drug Resistance Genes; Pvmdr1 and Pvcrt-o Polymorphisms in Relation to Chloroquine Sensitivity from a Malaria Endemic Area of Thailand
Korean J Parasitol. 2015;53(1):43-49.   Published online February 27, 2015
DOI: https://doi.org/10.3347/kjp.2015.53.1.43
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Plasmodium vivax Drug Resistance Genes; Pvmdr1 and Pvcrt-o Polymorphisms in Relation to Chloroquine Sensitivity from a Malaria Endemic Area of Thailand
Korean J Parasitol. 2015;53(1):43-49.   Published online February 27, 2015
DOI: https://doi.org/10.3347/kjp.2015.53.1.43
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Plasmodium vivax Drug Resistance Genes; Pvmdr1 and Pvcrt-o Polymorphisms in Relation to Chloroquine Sensitivity from a Malaria Endemic Area of Thailand
Plasmodium vivax Drug Resistance Genes; Pvmdr1 and Pvcrt-o Polymorphisms in Relation to Chloroquine Sensitivity from a Malaria Endemic Area of Thailand
Primer Sequence 5’ to 3’ nt position
Outer primer: mdrF: TTGAACAAGAAGGGGACGTT 82-101
mdrR: CTTATATACGCCGTCCTGCAC 4371-4351
crtF:GCTACCCCTAACGCACAATG -17-3
crtR: GATTTGGGAAAGCACAACGT 1853-1834
Nested primer: mdr1R:GCGTAAGATGCTAAAATGAACC 887-866
mdr2F:ATTTAACCTTTCAGAAAAGCTGT 783-805
mdr2R: CCACCTGACAACTTAGATGC 1748-1729
mdr3F: CTGATACAAGTGAGGAAGAACTAC 1600-1623
mdr3R: ACTATCCTGGTCAAAAAAGC 1757-1738
mdr4F: CCCTCTACATCTTAGTCATCG 2600-2620
mdr4R: TGGTCTGGACAAGTATCTAAAA 3531-3510
mdr5F: GGATAGTCATGCCCCAGGATTG 2751-2772
mdr5R: CATCAACTTCCCGGCGTAGC 3354-3335
mdr6F: GGAAGTTGATGTCCCTAAAGG 3344-3364
crtF:GATGAACGTTACCGGGAGTTGG 49-70
crtR: ATCGGAAGCATCAGGCAGGA 1772-1751
Amino acid residue at the codon indicated No. (%) of isolates with Pvmdr1 mutant alleles
S513R (agt/aga) 7 (23.3)
S515R (agc/agg) 30 (100)
T529 (aca/acg) T529 (aca) = 3 (10.0), T529 (acg) = 27 (90.0)
G698S (ggc/agc) 30 (100)
M908L (atg/ctg) 30 (100)
T958M (acg/atg) 30 (100)
Y976F (tac/ttc) 7 (23.3)
L1022 (cta/tta) L1022 (cta) = 30 (100)
F1076L (ttt/ctt) 16 (53.3)
Frequency distribution of the 5 haplotypes in Pvmdr1
 - 515R+ 698S+ 908L+ 958M (4 mutations) 8 (26.7)
 - 513R+ 515R+ 698S+ 908L+ 958M (5 mutations) 6 (20.0)
 - 515R+ 698S+ 908L+ 958M+ 1,076L (5 mutations) 8 (26.7)
 - 513R+ 515R+ 698S+ 908L+ 958M+1,076L (6 mutations) 1 (3.3)
 - 515R+ 698S+ 908L+ 958M + 976F+ 1,076L (6 mutations) 7 (23.3)
Median (range) Chloroquine IC50 (nM)
S513R S (n=12) 132.56 (39.99-243.17)
R (n=3) 141.99 (81.86-248.86)
S515R R (n=15) 137.04 (39.99-248.86)
T529 T (aca) (n=1) 43.24
T (acg) (n=14) 139.52 (39.99-248.86)
G698S S (n=15) 137.04 (39.99-248.86)
M908L L (n=15) 137.04 (39.99-248.86)
T958M M (n=15) 137.04 (39.99-248.86)
Y976F Y (n=13) 137.04 (39.99-248.86)
F (n=2) 165.19 (87.21-243.17)
L1022 L (cta) (n=15) 137.04 (39.99-248.86)
F1076L F (n=6) 119.41 (39.99-248.86)
L (n=9) 137.04 (43.24-243.17)
Chloroquine resistant Chloroquine sensitive
S513R S 7 5
R 2 1
S515R R 6 9
T529 T (aca) 0 1
T (acg) 9 5
G698S S 9 6
M908L L 9 6
T958M M 9 6
Y976F F 1 1
Y 8 5
L1022 L (cta) 9 6
F1076L F 3 3
L 6 3
Table 1. List of PCR primers for amplification of PvmdrI and Pvcrt-o genes
Table 2. Frequency distribution of mutation at each codon and haplotype in Pvmdr1 gene of 30 P. vivax isolates
Table 3. The polymorphisms in Pvmdr1 gene at the 4 highly polymorphic loci (S513R, Y976F, F1076L, and T529) including the other 5 loci and IC50 values of 15 selected P. vivax isolates with wild-type and mutant genotypes

Data are presented as number of isolates (n) and median (range) IC50 values.

Table 4. The association between polymorphisms in Pvmdr1 gene at the 4 highly polymorphic loci (S513R, Y976F, F1076L, T529) including the other 5 loci and in vitro susceptibilities of 15 selected P. vivax isolates to chloroquine classified based on the in vitro IC50 cut-off of 100 nM

Data are presented as number of isolates (n).

Table 1.

Table 2.

Table 3.

Table 4.

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