Table 5.
Genetic associations with detectable log10-transformed CSF:plasma 8-hydroxy-efavirenz concentrations in 16 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 | ||||
| 3 | ABCC5 | rs6762938 (T) | 0.31 | 0.23 (0.14–0.33) | 3.9 × 10−04 | 0.22 (0.12–0.32) | 1.1 × 10−03 | 0.22 (0.11–0.33) | 0.02 |
| 13 | ABCC4 | rs11343244 (T) | 0.10 | 0.41 (0.23–0.59) | 6.2 × 10−04 | 0.39 (0.20–0.49) | 1.1 × 10−03 | 0.41 (0.23–0.59) | 8.5 × 10−04 |
| 13 | ABCC4 | rs7997839 (G) | 0.14 | 0.41 (0.23–0.59) | 6.2 × 10−04 | 0.39 (0.20–0.49) | 1.1 × 10−03 | 0.41 (0.23–0.59) | 8.5 × 10−04 |
| 3 | ABCC5 | rs10937161 (T) | 0.20 | 0.36 (0.21–0.51) | 4.1 × 10−04 | 0.36 (0.22–0.49) | 2.3 × 10−04 | 0.35 (0.21–0.50) | 5.0 × 10−04 |
| 3 | ABCC5 | rs36092077 (A) | 0.16 | 0.39 (0.21–0.56) | 8.9 × 10−04 | 0.39 (0.23–0.54) | 3.7 × 10−04 | 0.39 (0.21–0.56) | 7.1 × 10−04 |
| 3 | ABCC5 | rs6807271 (A) | 0.31 | 0.21 (0.10–0.32) | 2.6 × 10−03 | 0.21 (0.10–0.32) | 2.6 × 10−03 | 0.20 (0.08–0.31) | 5.8 × 10−03 |
| 3 | ABCC5 | rs59309690 (A) | 0.09 | 0.60 (0.27–0.93) | 3.7 × 10−03 | 0.58 (0.26–0.90) | 4.1 × 10−03 | 0.57 (0.24–0.90) | 6.5 × 10−03 |
| 4 | ABCG2 | rs2728108 (A) | 0.08 | 0.60 (0.27–0.93) | 3.7 × 10−03 | 0.58 (0.26–0.90) | 4.1 × 10−03 | 0.57 (0.24–0.90) | 6.5 × 10−03 |
| 13 | ABCC4 | rs1678392 (A) | 0.19 | 0.32 (0.14–0.51) | 4.9 × 10−03 | 0.30 (0.11–0.50) | 0.01 | 0.31 (0.11–0.51) | 0.01 |
| 13 | ABCC4 | rs116336902 (A) | 0.07 | 0.32 (0.13–0.51) | 5.1 × 10−03 | 0.30 (0.10–0.50) | 0.01 | 0.31 (0.11–0.51) | 0.01 |
| 13 | ABCC4 | rs147385814 (C) | 0.07 | 0.32 (0.13–0.51) | 5.1 × 10−03 | 0.30 (0.10–0.50) | 0.01 | 0.31 (0.11–0.51) | 0.01 |
| 13 | ABCC4 | rs4771904 (T) | 0.27 | −0.27 (−0.44 to −0.10) | 7.8 × 10−03 | −0.26 (−0.45 to −0.07) | 0.02 | −0.27 (−0.44 to −0.10) | 0.03 |
| 3 | ABCC5 | rs6794223 (G) | 0.14 | 0.27 (0.10–0.43) | 6.7 × 10−03 | 0.25 (0.09–0.41) | 9.0 × 10−03 | 0.25 (0.08–0.42) | 0.01 |
| 11 | SLCO2B1 | rs57141326 (A) | 0.08 | 0.34 (0.12–0.56) | 9.6 × 10−03 | 0.31 (0.09–0.54) | 0.02 | 0.33 (0.11–0.56) | 0.02 |
| 7 | ABCB1 | rs28401781 (T) | 0.24 | 0.19 (0.07–0.32) | 9.0 × 10−03 | 0.19 (0.06–0.31) | 5.8 × 10−03 | 0.22 (0.11–0.33) | 2.4 × 10−03 |
| 3 | ABCC5 | rs56889675 (T) | 0.26 | 0.24 (0.09–0.38) | 7.6 × 10−03 | 0.27 (0.14–0.39) | 1.1 × 10−03 | 0.26 (0.13–0.39) | 2.1 × 10−03 |
| 3 | ABCC5 | rs10470524 (T) | 0.22 | 0.24 (0.09–0.38) | 7.6 × 10−03 | 0.27 (0.14–0.39) | 1.1 × 10−03 | 0.26 (0.13–0.39) | 2.1 × 10−03 |
| 13 | ABBC4 | rs4148551 (T) | 0.36 | −0.25 (−0.41 to −0.10) | 7.4 × 10−03 | −0.23 (−0.39 to −0.08) | 0.01 | −0.23 (−0.40 to −0.07) | 1.8 × 10−03 |
| 19 | CYP2B6 | composite CYP2B6 516/983 | 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 | −0.18 (−0.45–0.08) | 0.19 | NA | NA | NA | NA |
| 19 | CYP2B6 | CYP2B6 15582C→Tb | 0.10 | 0.02 (−0.24–0.28) | 0.88 | −0.05 (−0.33 to 0.22) | 0.70 | NA | NA |
| 19 | CYP2A6 | CYP2A6 −48A→Cb | 0.09 | −0.04 (−0.32–0.25) | 0.81 | 0.10 (−0.23 to 0.43) | 0.55 | 0.09 (−0.26–0.52) | 0.61 |
MAF, minor allele frequency; NA, not applicable.
For the CSF 8-hydroxy-efavirez analysis, the targeted SNPs (CYP2B6 516G→T, CYP2A6 -48A→C, CYP2B6 983T→C and CYP2B6 15582C→T) included 17 patients and the rest 16 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.