Table 3:
Association between variants in the atpE, pepQ, and Rv1979c Rv0678 gene and phenotypic resistance
| Phenotypic DST results | Statistical association between phenotype and genetic variant* | |||||||
|---|---|---|---|---|---|---|---|---|
| All | Clinical | Non-clinical | OR estimate (95% CI) | p value† | ||||
| R | S | R | S | R | S | |||
| atpE | ||||||||
| 187G→C | 11 | 0 | 1 | 0 | 10 | 0 | ∞ (13·28–∞) | <0·0001 |
| 83A→T | 2 | 0 | 0 | 0 | 2 | 0 | ∞ (0·93–∞) | 0·45 |
| 83A→C | 1 | 0 | 0 | 0 | 1 | 0 | ∞ (0·13–∞) | 0·73 |
| 72T→C | 1 | 0 | 1 | 0 | 0 | 0 | ∞ (0·13–∞) | 0·73 |
| 83A→G | 3 | 1 | 0 | 1 | 3 | 0 | 15·57 (1·24–14·22) | 0·45 |
| 183G→T | 0 | 1 | 0 | 1 | 0 | 0 | 0·00 (0–199·86) | 1·00 |
| 188C→T | 0 | 1 | 0 | 1 | 0 | 0 | 0·00 (0–197·73) | 1·00 |
| 196A→G, 53G→A, and 73G→A | 0 | 1‡ | 0 | 1‡ | 0 | 0 | 0·00 (0–92·59) | 1·00 |
| 183G→A (silent) | 0 | 1 | 0 | 1 | 0 | 0 | 0·00 (0–92·59) | 1·00 |
| 138T→C | 0 | 3 | 0 | 3 | 0 | 0 | 0·00 (0–2·01) | 1·00 |
| G82G→A | 0 | 4 | 0 | 4 | 0 | 0 | 0·00 (0–0·60) | 1·00 |
| Total | 18 | 14 | 2 | 14 | 16 | 0 | ·· | ·· |
| pepQ | ||||||||
| 811delC and 131T→C | 0 | 1‡ | 0 | 0 | 0 | 1‡ | 0·00 (0–230·84) | 1·00 |
| 324A→G, 352A→G, 538A→G, 706A→G, 31C→T, 1114C→G, 206C→T, 269C→T, 371C→T, 433C→A, 7C→T, 914C→T, 12G→C, 1108G→A, 274G→A, 278G→A, 641T→C, 454G→A, 500G→T, and 640G→T | 0 | 1‡ | 0 | 1‡ | 0 | 0 | 0·00 (0–30·84) | 1·00 |
| 42delC | 0 | 2 | 0 | 0 | 0 | 2 | 0·00 (0–1·67) | 1·00 |
| 1021A→G, 407A→G, 233C→T, 20G→A, 347G→T, and 925G→A | 0 | 2‡ | 0 | 2‡ | 0 | 0 | 0·00 (0–1·67) | 1·00 |
| Total | 0 | 34 | 0 | 30 | 0 | 4 | ·· | ·· |
| Rv1979c | ||||||||
| 733A→C | 1 | 0 | 1 | 0 | 0 | 0 | ∞ (0·19–∞) | 0·73 |
| 1226G→A | 2 | 37 | 2 | 37 | 0 | 0 | 0·39 (0·05–1·58) | 1·00 |
| 114G→C | 1 | 23 | 1 | 23 | 0 | 0 | 0·32 (0·01–0·01) | 1·00 |
| 155A→C, 562C→T, 1216G→A, 724G→A, 1057T→G, 311T→C, and 824T→C | 0 | 1‡ | 0 | 1‡ | 0 | 0 | 0·00 (0–291·36) | 1·00 |
| 1403A→G, 20G→A, 187A→G, 1432C→G, and 520C→T | 0 | 2‡ | 0 | 2‡ | 0 | 0 | 0·00 (0–40·09) | 1·00 |
| 798G (silent) | 0 | 2 | 0 | 2 | 0 | 0 | 0·00 (0–40·09) | 1·00 |
| 114G→T or C | 0 | 8 | 0 | 8 | 0 | 0 | 0·00 (0–4·42) | 1·00 |
| 151T→A | 0 | 14 | 0 | 14 | 0 | 0 | 0·00 (0–2·26) | 1·00 |
| 857A→G | 0 | 22 | 0 | 22 | 0 | 0 | 0·00 (0–1·36) | 0·73 |
| Total | 3 | 121 | 3 | 121 | 0 | 0 | ·· | ·· |
The variants that are observed only in resistant isolates are shown on top, with variants that are observed only in susceptible isolates are shown on the bottom of the table.
To be included studies had to report at a minimum on variants in both the Rv0678 and atpE genes and co-occurring mutations could not be present in phenotypically resistant isolates. Del=deletion. DST=drug susceptibility test. Ins=insertion. OR=odds ratio. R=resistant. S=susceptible.
Statistical analysis using the standardised method published by Miotto and colleagues.24
p value adjusted for false discovery rate for all missense single nucleotide polymorphism; p values were not adjusted for insertions, deletions, silent mutations, and non-sense mutations.
n represents the number of strains reported with each of the unique variants listed.