Table S2.
Pharmacokinetic parameters and lipid-lowering response of SLCO1B1 c.-910G>A, SLCO1B3 c.334G>T, and ABCC2 c.1249G>A
| Variable | Unit | Genotype | FC (95% CI) | P-value | ||
|---|---|---|---|---|---|---|
| SLCO1B1 c.-910G>A | G/G | G/A | A/A | |||
| n | 33 | 14 | 3 | |||
| AUC∞ | ng⋅h/mL | 156±80.5a (51.5%) (48.9–403) |
173±79.7 (46.0%) (86.2–334) |
333±181 (54.4%) (147–509) |
1.00 (0.77–1.31)b 1.89 (0.39–9.10)c |
0.077 |
| CLadj | L/(h⋅kg) | 9.54±4.90 (51.4%) (2.48–25.2) |
8.01±3.38 (42.3%) (2.85–15.0) |
5.11±3.61 (70.6%) (2.46–9.22) |
0.77 (0.59–1.00) 0.46 (0.08–2.46) |
0.099 |
| Cmax | ng/mL | 33.5±16.7 (49.7%) (9.50–81.6) |
34.0±14.9 (43.8%) (10.9–69.7) |
76.5±26.4 (34.4%) (46.1–92.2) |
0.92 (0.71–1.21) 2.18 (0.81–5.84) |
0.021 |
| %ΔTC | % | −10.0±11.6 (−117%) (−31.9 to 11.8) |
−10.7±8.23 (−76.9%) (−27.7 to 4.00) |
−10.1±7.36 (−73.1%) (−16.6 to −2.10) |
0.992 | |
| %ΔTG | % | 14.4±74.3 (518%) (−68.1 to 258) |
−16.6±34.5 (−208%) (−62.5 to 34.4) |
1.70±16.8 (986%) (−10.6 to 20.8) |
0.659 | |
| %ΔLDL-C | % | −13.7±23.5 (−172%) (−58.2 to 36.0) |
−17.6±14.5 (−82.4%) (−45.6 to 7.40) |
−19.5±14.8 (−75.7%) (−29.1 to −2.50) |
0.948 | |
| SLCO1B3 c.334G>T | G/G | G/T | T/T | |||
| n | 28 | 16 | 6 | |||
| AUC∞ | ng⋅h/mL | 151±86.8 (57.4%) (48.9–403) |
172±68.9 (40.1%) (97.6–334) |
267±142 (53.2%) (126509) |
1.06 (0.86–1.30)b 1.57 (0.91–2.72)c |
0.069 |
| CLadj | L/(h⋅kg) | 10.1±5.27 (52.0%) (2.48–25.2) |
7.72±2.55 (33.0%) (2.85–11.9) |
5.85±3.00 (51.3%) (2.46–9.74) |
0.72 (0.59–0.88) 0.51 (0.29–0.90) |
0.109 |
| Cmax | ng/mL | 31.4±15.7 (49.9%) (9.50–65.4) |
34.7±15.5 (44.6%) (10.9–81.6) |
63.0±25.0 (39.6%) (36.6–92.2) |
1.01 (0.80–1.28) 1.88 (1.21–2.87) |
0.010 |
| %ΔTC | % | −8.27±12.1 (−147%) (−31.2 to 11.8) |
−12.1±6.93 (−57.1%) (−31.9 to 1.80) |
−13.9±8.90 (−64.1%) (−27.7 to −2.10) |
0.070 | |
| %ΔTG | % | 12.5±78.3 (625%) (−68.1 to 257.5) |
−0.79±43.4 (−5,470%) (−62.5 to 128) |
−15.3±28.5 (−187%) (−57.7 to 20.8) |
0.770 | |
| %ΔLDL-C | % | −11.4±25.9 (−227%) (−58.2 to 36.0) |
−16.9±6.05 (−35.7%) (−26.8 to −3.40) |
−27.3±14.0 (−51.2%) (−45.6 to −2.50) |
0.201 | |
| ABCC2 c.1249G>A | G/G | G/A | ||||
| n | 43 | 7 | ||||
| AUC∞ | ng⋅h/mL | 172±92.1 (53.6%) (48.9–509) |
170±119 (69.7%) (58.2–342) |
0.80 (0.42–1.53)b | 0.547 | |
| CLadj | L/(h⋅kg) | 8.69±4.30 (49.5%) (2.46–25.2) |
9.81±6.15 (62.7%) (2.71–18.6) |
0.92 (0.47–1.81) | 0.412 | |
| Cmax | ng/mL | 35.7±17.9 (50.3%) (9.70–92.2) |
39.8±28.1 (70.6%) (9.50–91.3) |
0.88 (0.43–1.81) | 0.642 | |
| %ΔTC | % | –11.9±9.81 (−82.7%) (−31.9 to 9.80) |
0.23±8.11 (3,549%) (−8.70 to 11.8) |
0.003 | ||
| %ΔTG | % | 1.30±62.3 (4,789%) (−68.1 to 258) |
27.2±77.0 (283%) (−62.5 to 156) |
0.452 | ||
| %ΔLDL-C | % | −17.4±20.3 (−117%) (−58.2 to 36.0) |
−0.70±18.0 (−2,565%) (−26.6 to 25.2) |
0.023 |
Notes:
Mean ± SD (CV) (range) of each variable according to genotype.
Fold change in heterozygotes compared to major homozygotes.
Fold change in minor homozygotes compared to major homozygotes.
Abbreviations: AUC∞, area under the plasma concentration curve from hour 0 to infinity; CI, confidence interval; CLadj, clearance adjusted with body weight; Cmax, maximum drug concentration in plasma; CV, coefficient of variation; FC, fold change; %ΔLDL-C, percentage change in low-density lipoprotein cholesterol from baseline to 48 hours after atorvastatin administration; SD, standard deviation; %ΔTC, percentage change in total cholesterol from baseline to 48 hours after atorvastatin administration; %ΔTG, percentage change in triglycerides from baseline to 48 hours after atorvastatin administration.