TABLE 3.
Associations between SNPs or indels in 10 putative transporter genes and IC50s for eight antimalarial drugsa
Gene | Predicted product | Position | Amino acid changeb | Nucleotide changec | N | Freq. common variantd |
P value
|
|||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CQ | QN | AQ | AS | LUM | DHA | DOX | MFQ | |||||||
pfmdr | ABC transporter | 86 | N-Y | AAT-TAT | 108 | 104 | 0.357 | 0.646 | 0.992 | 0.576 | 0.809 | 0.843 | 0.717 | 0.079 |
184 | Y-F | TAT-TTT | 105 | 61 | 0.405 | 0.040 | 0.374 | 0.025 | 0.134 | 0.970 | 0.568 | 0.020 | ||
1034 | S-C | AGT-TGT | 107 | 107 | NI | NI | NI | NI | NI | NI | NI | NI | ||
1042 | N-D | AAT-GAT | 108 | 98 | 0.778 | 0.063 | 0.635 | 0.144 | 0.000 | 0.270 | 0.763 | 0.000 | ||
1246 | D-Y | GAT-TAT | 106 | 105 | NI | NI | NI | NI | NI | NI | NI | NI | ||
G2 | ABC transporter | 191 | Y-H | TAT-CAT | 107 | 107 | NI | NI | NI | NI | NI | NI | NI | NI |
437 | A-S | GCA-TCA | 105 | 90 | 0.149 | 0.795 | 0.540 | 0.995 | 0.304 | 0.093 | 0.426 | 0.768 | ||
G7 | ABC transporter | 1390 | &1 | NA | 104 | 96 | 0.061 | 0.015 | 0.622 | 0.042 | 0.450 | 0.258 | 0.712 | 0.246 |
G25 | Sulfate transporter | Intron | G-A | G-A | 101 | 77 | 0.771 | 0.838 | 0.224 | 0.702 | 0.138 | 0.624 | 0.071 | 0.579 |
G30 | GTPase | Intron | C-G | C-G | 108 | 104 | 0.289 | 0.870 | 0.485 | 0.106 | 0.638 | 0.091 | 0.977 | 0.272 |
G47 | Glycine transporter | 241 | L-V | TTA-GTA | 105 | 94 | 0.386 | 0.085 | 0.315 | 0.389 | 0.284 | 0.702 | 0.995 | 0.799 |
G49 | ABC/ATPase | 146 | Q-E | CAA-GAA | 108 | 66 | 0.696 | 0.937 | 0.711 | 0.606 | 0.299 | 0.117 | 0.145 | 0.988 |
1046 | K-I | AAA-ATA | 108 | 78 | 0.260 | 0.349 | 0.638 | 0.316 | 0.401 | 0.831 | 0.457 | 0.817 | ||
1116 | L-I | TTA-ATA | 108 | 96 | 0.063 | 0.714 | 0.435 | 0.293 | 0.514 | 0.002 | 0.187 | 0.867 | ||
G54 | Membrane protein | 141 | Y-Y | TAC-TAT | 102 | 54 | 0.209 | 0.904 | 0.194 | 0.848 | 0.165 | 0.751 | 0.443 | 0.965 |
144 | T-T | ACG-ACA | 102 | 54 | 0.209 | 0.904 | 0.194 | 0.848 | 0.165 | 0.751 | 0.443 | 0.965 | ||
G55 | ABC transporter | Intron | &2 | NA | 107 | 60 | 0.227 | 0.212 | 0.475 | 0.414 | 0.161 | 0.608 | 0.429 | 0.938 |
G70 | Choline transporter | 105 | E-K | GAA-AAA | 102 | 52 | 0.535 | 0.292 | 0.866 | 0.225 | 0.497 | 0.865 | 0.195 | 0.557 |
Pfcrt is not included in the table because it was monomorphic in all but one isolate examined. Drug abbreviations are as described in the text. We used t tests to compare IC50s in parasites with polymorphisms, and significant results (P < 0.05) are shown in bold. Both polymorphism data and IC50s are listed in the supplemental material online. Comparisons that were significant in Mu et al.'s southeast Asian data set (14) are shown underlined (CQ and QN columns only).
&1 is a 3-bp indel. &2 is a dinucleotide microsatellite in an intron. We found four alleles. For this analysis, alleles were grouped into those that were ≤194 and ≥196. Some loci showed insufficient variation (<2 alleles with one allelic state); these are labeled NI.
NA, not applicable.
Frequency of common variant.