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Table 4 Association between piperaquine (PPQ) resistance mutations (SNPs as well as copy number variation (CNV)) with in vitro PPQ IC50s of Kenyan field isolates collected between 2008 and 2021

From: Impact of parasite genomic dynamics on the sensitivity of Plasmodium falciparum isolates to piperaquine and other antimalarial drugs

In vitro SYBR Green I assay

Gene Polymorphisms/Assay

 

N

Proportions

(%)

PPQ median IC50 (IQR) nM

P value

P. falciparum multidrug resistance 1 gene, Pfmdr1

SNPs

N86

34

75.6

23.5 (12.7–44.4)

0.26

86N/Y

6

13.3

34.9 (22.0–80.5)

 

86Y

5

11.1

29.9 (26.5–288.5)

 

Y184

22

47.8

29.5 (21.1–39.0)

0.55

184Y/F

6

13.0

26.9 (9.2–80.7)

 

184F

18

39.1

23.9 (11.4–45.0)

 

A1034

34

85.0

29.7 (21.1–39.0)

 0.81

1034T

6

15.0

30.3 (10.3–279.4)

 

P. falciparum chloroquine resistance transporter 1 gene, Pfcrt

SNPs

K76

25

65.8

18.9 (10.1–31.9)

0.0026**

76K/T

5

13.2

36.6 (26.1–249.9)

 

76T

8

21.0

33.8 (22.2–73.2)

 

T356

9

37.5

18.9 (7.7–42.6)

0.73

356C

15

62.5

15.7 (6.5–29.5)

 

G371

10

64.3

16.6 (8.0–30.3)

0.96

371T

18

35.7

20.2 (9.2–31.2)

 

P. falciparum dihydrofolate reductase gene, Pfdhfr

SNPs

C59

4

11.8

18.3 (7.8–69.1)

0.98

59R

30

88.2

22.4 (1.7–33.4)

 

I164

30

92.3

23.2 (10.8–33.4)

0.58

P. falciparum dihydropteroate synthetase gene, Pfdhps

SNPs

164L

2

7.7

30.3 (18.3–42.2)

 

S436

16

84.2

22.4 (11.8–34.7)

0.88

436F

3

15.8

18.9(2.2–416.1)

 

A437

19

73.1

20.2 (8.8–32.7)

0.33

437G

7

26.9

31.4 (22.4–36.6)

 

P. falciparum multidrug resistance 1 gene, Pfmdr1

CNV

Single copy

271

96.8

29.9 (14.4–47.4)

0.48

Multiple copies

9

3.2

46.1 (12.1–99.9)

 

P. falciparum plasmepsin 2 gene, Pfpm2

CNV

Single copy

280

97.9

29.9 (14.4–47.2)

0.63

Multiple copies

6

2.1

44.6 (18.3 –71.0)

 

P. falciparum plasmepsin 3 gene, Pfpm3

CNV

Single copy

276

92.9

30.0 (14.5–47.6)

0.72

Multiple copies

20

7.1

31.3 (19.6–48.2)

 
  1. ** Show P < 0.05 consistent with statistically significant differences in frequency over time using Kruskal-Wallis (H) tests for three groups and Mann-Whitney (U) test for two groups