Table 5.
Relations between CYP2C19, CYP2D6, CYP3A5 and SULT1A1 genotypes and estrogens in postmenopausal women (n = 90)
| Median concentration [q1 - q3] 1 | |||||
|---|---|---|---|---|---|
| Genotype (n) | E1 | E2 | E1S | ||
| CYP2C192 | *2/*2 | (4) | 122 [88 - 303] | 9.6 [6.7 - 43.5] | 857 [309 - 1400] |
| *1/*2 | (15) | 106 [72 - 182] | 13.0 [6.6 - 32.0] | 391 [234 - 955] | |
| *1/*1 | (35) | 102 [70 - 124] | 10.9 [5.7 - 16.0] | 655 [345 - 928] | |
| Vt*17 | (33) | 86 [66 - 104] | 8.4 [6.0 - 12.1] | 545 [259 - 801] | |
| *17/*17 | (3) | 75 [54 - 122] | 9.3 [9.3 - 17.4] | 428 [158 - 654] | |
| P3 | 0.019* | 0.139 | 0.227 | ||
| CYP2D64 | PM | (6) | 111 [96 - 154] | 9.4 [6.6 - 24.4] | 491 [318 - 878] |
| IM | (32) | 91 [66 - 111] | 7.7 [5.2 - 14.1] | 595 [255 - 931] | |
| Wt/Wt | (51) | 101 [67 - 128] | 10.9 [6.1 - 17.4] | 588 [345 - 888] | |
| UM | (1) | 72 | 6.6 | 391 | |
| P | 0.559 | 0.938 | 0.804 | ||
| CYP3A5 | Vt/Vt | (76) | 99 [71 - 123] | 10.5 [6.6 - 16.4] | 569 [305 - 865] |
| Wt/Vt | (14) | 97 [65 - 124] | 8.0 [4.3 - 10.5] | 631 [294 - 1127] | |
| P | 0.520 | 0.248 | 0.221 | ||
| SULT1A1 | Vt/Vt | (14) | 80.6 [66.4- 103.5] | 6.7 [5.2- 9.4] | 590.4 [316.5- 851.1] |
| Wt/Vt | (32) | 99.1 [68.6-121.7] | 13.7 [5.3-18.9] | 537.0 [318.0- 768.7] | |
| Wt/Wt | (44) | 102.1 [70.9-142.1] | 9.4 [1.4-54.7] | 608.5 [135.6-2922.9] | |
| P | 0.280 | 0.575 | 0.734 | ||
| SULT1A1copy numbers | 1 | (3) | 59.7 [58.7-101.2] | 3.8 [2.6- 6.5] | 252.9 [235.5- 939.0] |
| 2 | (59) | 89.8 [67.2-110.2] | 7.7 [5.5-15.2] | 498.4 [271.6- 758.9] | |
| 3 | (21) | 105.7 [90.7-128.6] | 11.8 [9.0-14.3] | 859.5 [561.3- 955.2] | |
| 4 | (5) | 101.8 [98.0- 103.0] | 15.3 [12.6-19.1] | 363.6 [227.5- 662.0] | |
| 5 | (2) | 157.6 [155.3-160.0] | 13.6 [9.4-17.9] | 2086.3 [1780.7-2391.9] | |
| P | 0.024* | 0.010* | 0.005** | ||
1Median concentration [quartile 1 - quartile 3] values of tamoxifen and metabolites are given as ng/ml.
2*2/*2, encodes defective CYP2C19 activity; Vt*17, subjects heterozygous for the variant type allele CYP2C19*17 (*1/*17 and *2/*17); *17/*17, encodes ultra rapid CYP2C19 activity.
3P values were calculated by multivariate logistic regression model, *p < 0.05. Adjusted for CYP2C19, CYP2D6, CYP3A5, SULT1A1, SULT1A1 copy number, FSH and SHBG.
4PM, poor metabolizer; IM, wild type/variant type; Wt/Wt, wild type/wild type; UM, ultra rapid metabolizer.