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Table 3 Polymorphisms and genotype clusters with significant effect on ATV pharmacokinetics

From: A pharmacogenetic pilot study reveals MTHFR, DRD3, and MDR1 polymorphisms as biomarker candidates for slow atorvastatin metabolizers

   Pharmacokinetics parameters
Genotypes N Cmax (ng/mL) AUC0-t (ng/mL*h) AUC0-∞ (ng/mL*h) Cl/F (L/h) T1/2 (h) Ke
MTHFR rs1801133
 C/C 14 60.46 ± 20.60 195.77 ± 91.84 213.25 ± 94.16 448.86 ± 202.58 12.95 ± 9.30 0.07 ± 0.04
 C/T 37 44.81 ± 24.32* 152.83 ± 87.67 166.43 ± 86.52 595.20 ± 274.47 10.78 ± 5.84 0.08 ± 0.04
 T/T 9 34.89 ± 12.90** 141.64 ± 66.29 151.57 ± 67.28 623.70 ± 287.68 9.94 ± 4.19 0.08 ± 0.03
 C/T + T/T 46 42.87 ± 22.77§ 150.64 ± 83.37§ 163.52 ± 82.64§ 600.77 ± 274.06§ 10.62 ± 5.52 0.08 ± 0.03
DRD3 rs6280
 C/C 17 39.90 ± 14.47 149.50 ± 59.86 159.43 ± 57.99 562.72 ± 200.54 8.63 ± 2.33¢ 0.08 ± 0.02¢
 C/T 26 44.12 ± 23.77 143.60 ± 85.50 156.77 ± 86.61 654.34 ± 316.38 10.67 ± 6.65 0.09 ± 0.04
 T/T 17 58.41 ± 26.70# 199.72 ± 102.65§§, # 218.89 ± 100.70§§, # 431.78 ± 177.83§§, # 14.44 ± 8.15§§, # 0.06 ± 0.03§§, #
 C/C + C/T 43 42.45 ± 20.51 145.93 ± 75.66 157.83 ± 75.82 618.12 ± 277.41 9.86 ± 5.43 0.09 ± 0.04
GSTM3 rs1799735
 *A/*A 55 44.71 ± 21.36 158.00 ± 89.57 171.60 ± 90.03 582.27 ± 270.90 10.92 ± 6.24 0.08 ± 0.03
 *A/*B 5 71.92 ± 32.15 196.08 ± 33.24 213.93 ± 28.26¥ 378.87 ± 46.77¥ 13.82 ± 10.17 0.08 ± 0.07
TNF rs1800629
 G/G 51 45.54 ± 22.80 153.18 ± 82.16 167.14 ± 83.12 586.66 ± 266.42 10.59 ± 6.14 0.08 ± 0.04
 G/A 9 55.88 ± 26.94 215.85 ± 96.68 230.57 ± 93.37 391.55 ± 132.91 14.66 ± 8.45 0.06 ± 0.02
MDR1 rs1045642
 C/C 13 33.43 ± 13.40 135.68 ± 78.72 150.53 ± 79.10 699.77 ± 376.59 10.87 ± 4.99 0.08 ± 0.04
 C/T + T/T 47 50.78 ± 24.21¤ 168.22 ± 88.36 181.93 ± 88.95 528.14 ± 216.66 11.24 ± 7.00 0.08 ± 0.03
SLCO1B1 rs4149056
 C/C + C/T 11 53.92 ± 24.72 222.27 ± 91.48 241.23 ± 92.98 390.51 ± 195.46 12.42 ± 8.59 0.07 ± 0.03
 T/T 49 45.41 ± 23.01 147.45 ± 80.40 160.29 ± 79.55 604.57 ± 264.87 10.88 ± 6.12 0.08 ± 0.04
P-values of genotype combinations on ATV pharmacokinetics
Clusters   Cmax AUC0-t AUC0-∞ Cl/F T1/2 Ke
A vs. B   0.163 0.060 0.041£ 0.041£ 0.519 0.519
B vs. C   0.007£ 4 × 10−4£ 0.001£ 0.001£ 0.177 0.177
A vs. C   0.016£ 0.011£ 0.011£ 0.011£ 0.181 0.181
C vs. A + B   0.001£ 9.1 × 10−5£ 1.31 × 10−4£ 9.5 × 10−5£ 0.112 0.399
D vs. E   0.187 0.060 0.041£ 0.002£ 0.610 0.486
E vs. F   2.3 × 10−4£ 0.001£ 0.001£ 0.004£ 0.241 0.260
D vs. F   1 × 10−3£ 0.014£ 0.011£ 6 × 10−6£ 0.230 0.177
F vs. D + E   5.3 × 10−5£ 3.61 × 10−4£ 4.22 × 10−4£ 1.35 × 10−4£ 0.115 0.176
  1. Data presented as mean ± standard deviation
  2. *P = 0.018 (C/T vs. C/C), **P = 0.004 (T/T vs. C/C), §P ≤ 0.050 (C/T + T/T vs. C/C), §§P ≤ 0.041 (T/T vs. C/T), ¢P ≤ 0.008 (C/C vs. T/T), #P ≤ 0.050 (T/T vs. C/C + C/T), ¥P = 0.041 (*A/*B vs. *A/*A), P ≤ 0.035 (G/A vs. G/G), ¤P = 0.037 (C/T + T/T vs. C/C), P = 0.004 (T/T vs. C/C + C/T), £ = significant. Clusters are explained in the main text