Table 4.
Genetic associations with detectable log10-transformed CSF:plasma efavirenz concentrations in South African adults
| Chromosome | Gene | Polymorphism (minor allele) | MAF | 516G→T adjusted |
516G→T and 983T→C adjusted |
516G→T and 983T→C and CYP2B6 15582C→T adjusted |
|||
|---|---|---|---|---|---|---|---|---|---|
| β (95% CI) | P | β (95% CI) | P | β (95% CI) | P | ||||
| 13 | ABCC4 | rs9584273 (T) | 0.07 | 0.14 (0.06–0.22) | 2.2 × 10−03 | 0.14 (0.05–0.22) | 2.8 × 10−03 | 0.14 (0.06–0.22) | 2.5 × 10−03 |
| 13 | ABCC4 | rs9590160 (A) | 0.09 | −0.12 (−0.19 to −0.04) | 3.2 × 10−03 | −0.12 (−0.19 to −0.04) | 3.5 × 10−03 | −0.12 (−0.19 to −0.04) | 4.3 × 10−03 |
| 13 | ABCC4 | rs74107818 (G) | 0.10 | −0.11 (−0.18 to −0.04) | 3.2 × 10−03 | −0.11 (−0.19 to −0.04) | 3.3 × 10−03 | −0.11 (−0.18 to −0.04) | 4.0 × 10−03 |
| 13 | ABCC4 | rs74107809 (A) | 0.07 | −0.13 (−0.21 to −0.04) | 5.8 × 10−03 | −0.13 (−0.21 to −0.04) | 4.8 × 10−03 | −0.13 (−0.21 to −0.04) | 5.7 × 10−03 |
| 19 | CYP2B6 | rs8100458 (C) | 0.19 | 0.07 (0.02–0.12) | 6.8 × 10−03 | 0.08 (0.03–0.14) | 6.4 × 10−03 | 0.10 (0.03–0.16) | 5.4 × 10−03 |
| 3 | ABCC5 | rs7610724 (G) | 0.07 | 0.10 (0.03–0.18) | 7.7 × 10−03 | 0.10 (0.03–0.17) | 7.6 × 10−03 | 0.11 (0.03–0.18) | 9.8 × 10−03 |
| 7 | ABCB1 | rs2235023 (T) | 0.42 | −0.06 (−0.11 to −0.02) | 7.8 × 10−03 | −0.06 (−0.11 to −0.02) | 7.6 × 10−03 | −0.06 (−0.11 to −0.02) | 9.2 × 10−03 |
| 19 | CYP2G1P | rs142357867 (T) | 0.03 | −0.16 (−0.28 to −0.05) | 8.9 × 10−03 | −0.17 (−0.29 to −0.06) | 5.5 × 10−03 | −0.18 (−0.30 to −0.06) | 5.1 × 10−03 |
| 13 | ABCC4 | rs200689258 (AC) | 0.09 | 0.11 (0.03–0.19) | 8.0 × 10−03 | 0.11 (0.03–0.18) | 0.01 | 0.11 (0.03–0.19) | 0.01 |
| 3 | ABCC5 | rs7427051(A) | 0.24 | −0.07 (−0.11 to −0.02) | 8.6 × 10−03 | −0.07 (−0.12 to −0.02) | 0.01 | −0.07 (−0.12 to −0.02) | 0.01 |
| 13 | ABCC4 | rs73548889 (C) | 0.06 | 0.13 (0.04–0.22) | 9.9 × 10−03 | 0.13 (0.03–0.22) | 0.01 | 0.14 (0.05–0.24) | 6.9 × 10−03 |
| 13 | ABCC4 | rs9524925 (G) | 0.17 | −0.07 (−0.12 to −0.02) | 7.6 × 10−03 | −0.07 (−0.13 to −0.02) | 0.01 | −0.07 (−0.12 to −0.02) | 0.01 |
| 19 | CYP2B6 | composite CYP2B6 516/983 (C) | 0.41 | NA | NA | NA | NA | NA | NA |
| 19 | CYP2B6 | CYP2B6 516G→Ta | 0.29 | NA | NA | NA | NA | NA | NA |
| 19 | CYP2B6 | CYP2B6 983T→Cb | 0.13 | −0.03 (−0.10–0.06) | 0.60 | NA | NA | NA | NA |
| 19 | CYP2B6 | CYP2B6 15582C→Tb | 0.10 | −0.03 (−0.10–0.07) | 0.68 | −0.03 (−0.12–0.07) | 0.57 | NA | NA |
| 19 | CYP2A6 | CYP2A6 −48A→Cb | 0.09 | −0.00 (−0.09–0.09) | 0.97 | 0.01 (−0.09–0.12) | 0.78 | 0.01 (−0.09–0.12) | 0.80 |
MAF, minor allele frequency; NA, not applicable.
The targeted SNPs (CYP2B6 516G→T, CYP2A6 −48A→C, CYP2B6 983T→C, CYP2B6 15582C→T, SLCO1B1 521T→ C and SLCO1B1) included 47 patients and the rest 43 patients.
a
P < 0.05 accepted as significant for SNPs with a previously described association.
b
SNP of interest but did not meet criteria of P < 0.01; Bonferroni-corrected P value 5.68 × 10−05.