Polymorphism in the Plasmodium falciparum chloroquine-resistance transporter protein links verapamil enhancement of chloroquine sensitivity with the clinical efficacy of amodiaquine

Table 8 Prediction of DAQ IC50 nM value for CQ-resistant lines on the basis of mean EIS for the 72-76 haplotype and the linear equation in Fig. 1. (IC50 nM = -73.459(mean EIS) + 69.775).

EIS	C5K76I Laboratory	C34Dd2 SE Asia	C67G8Brazil	Jav/IAJColombia	Ecu1110 Ecuador	Cambodia	Cambodia	Cambodia
HAPLO.	CIEI	CIET	SMNT	CMET	CMNT	CMNT	CIDT	CTNT
72	0.04	0.04	-0.26	0.04	0.04	0.04	0.04	0.04
74	0.73	0.73	0.26	0.26	0.26	0.26	0.73	-0.18
75	-0.62	-0.62	-0.64	-0.62	-0.64	-0.64	-0.72	-0.64
76	0.73	-0.18	-0.18	-0.18	-0.18	-0.18	-0.18	-0.18
SUM	0.88	-0.03	-0.82	-0.5	-0.52	-0.52	-0.13	-0.96
MEAN	0.22	-0.0075	-0.205	-0.125	-0.13	-0.13	-0.0325	-0.24
predict IC50 DAQ (nM)	53.6	70.3	84.8	79.0	79.3	79.3	72.2	87.4
ACTUAL	54.8	69.05	86.2
PGH-1 factor	Y86---N86	Y86---N86	S. America	S. America	S. America	Y86---N86	Y86---N86	Y86---N86
	1.4------1.0	1.4------1.0	----------2.7	----------2.7	----------2.7	1.4------1.0	1.4------1.0	1.4------1.0
predict field sensitivity (IC50) nM
IC50 DAQ (nM)	76-------54	98-------70	---------230	---------213	---------213	111------79	101-----72	122-----87

(To adjust for the PGH-1 factor, derived from the study of Sidhu et al, 2002 [16], multiply by 1.4 where N86Y is found in Africa and SE Asia, and 2.7 for the usual S. American pfmdr1 haplotype of S1034C, N1042D, D1246Y [27].)

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