Functional Polymorphisms | Number of Subjects | UGT Activities | UGT Protein Content | ||||||
---|---|---|---|---|---|---|---|---|---|
SN-38G | Bilirubin-G | E2-3G | UGT1A1 Protein Expression | UGT1A9 Protein Expression | |||||
pmol/min/mg | nmol/min/mg | arbitrary units | |||||||
UGT1A1 | |||||||||
UGT1A1 -53 | |||||||||
*1/*1 | 24 | 63.2 ± 43.4 | 0.79 ± 0.46 | 0.38 ± 0.28 | 19.7 ± 8.4 | ||||
*1/*28 | 17 | 51.2 ± 45.9 | 0.58 ± 0.40 | 0.33 ± 0.29 | 15.0 ± 10.9 | ||||
*28/*28 | 7 | 36.6 ± 49.2* | 0.47 ± 0.68* | 0.22 ± 0.42* | 8.3 ± 9.6* | ||||
p valuea | 0.02 | 0.01 | 0.01 | 0.003 | |||||
UGT1A1 -3156 | |||||||||
G/G | 29 | 64.2 ± 44.9 | 0.79 ± 0.46 | 0.38 ± 0.29 | 19.9 ± 8.4 | ||||
G/A | 12 | 43.6 ± 40.9 | 0.48 ± 0.33 | 0.31 ± 0.27 | 12.7 ± 10.9* | ||||
A/A | 7 | 36.6 ± 49.2* | 0.47 ± 0.68* | 0.22 ± 0.42* | 8.3 ± 9.6* | ||||
p valuea | 0.01 | 0.006 | 0.01 | 0.0006 | |||||
UGT1A1 -3279 | |||||||||
T/T | 13 | 65.5 ± 40.5 | 0.81 ± 0.34 | 0.43 ± 0.29 | 21.3 ± 6.7 | ||||
G/T | 22 | 62.6 ± 49.3† | 0.69 ± 0.52 | 0.34 ± 0.30 | 17.4 ± 11.3† | ||||
G/G | 13 | 31.9 ± 35.9* | 0.49 ± 0.52* | 0.25 ± 0.32* | 9.9 ± 7.8* | ||||
p valuea | 0.004 | 0.01 | 0.03 | 0.002 | |||||
UGT1A9 | |||||||||
UGT1A9 -118 | |||||||||
T9/9 | 18 | 39.2 ± 36.6 | 0.49 ± 0.45 | 0.25 ± 0.29 | 12.0 ± 8.7 | 7.7 ± 3.0 | |||
T9/10 | 22 | 63.1 ± 48.0 | 0.72 ± 0.50 | 0.35 ± 0.29 | 18.3 ± 11.2 | 8.6 ± 3.2 | |||
T10/10 | 8 | 68.7 ± 49.5 | 0.94 ± 0.40* | 0.50 ± 0.34* | 21.2 ± 6.3* | 8.9 ± 3.0 | |||
p valuea | 0.05 | 0.02 | 0.03 | 0.03 | 0.5 | ||||
UGT1A9 -275 | |||||||||
T/T | 41 | 56.5 ± 46.0 | 7.8 ± 2.8 | ||||||
T/A | 7 | 46.6 ± 41.7 | 11.2 ± 3.4 | ||||||
A/A | 0 | ||||||||
p valueb | 0.6 | 0.006 | |||||||
UGT1A9 -2152c | |||||||||
C/C | 43 | 55.5 ± 45.2 | 7.8 ± 2.7 | ||||||
C/T | 5 | 51.0 ± 49.9 | 12.7 ± 2.5 | ||||||
T/T | 0 | ||||||||
p valueb | 0.7 | 0.0004 | |||||||
UGT1A9 I399d | |||||||||
C/C | 17 | 33.9 ± 25.2 | 0.48 ± 0.29 | 0.20 ± 0.20 | 13.5 ± 7.4 | 7.5 ± 3.0 | |||
C/T | 20 | 54.1 ± 41.3 | 0.64 ± 0.48 | 0.37 ± 0.33* | 15.4 ± 10.5 | 8.1 ± 2.5 | |||
T/T | 11 | 89.5 ± 57.0* | 1.01 ± 0.58* | 0.50 ± 0.33* | 22.7 ± 11.3* | 10.1 ± 3.7* | |||
p valuea |
| 0.007 | 0.05 | 0.006 | 0.12 | 0.08 |
↵* Significantly different (Student's t test) from the corresponding homozygote reference group (p < 0.05).
↵† Significantly different (Student's t test) from the corresponding homozygote mutant group (p < 0.05). All other genotype-phenotype relationships were nonsignificant (p > 0.05).
↵ a Analysis of variance.
↵ b Student's t test.
↵ c Alleles with -2152T also included polymorphisms at positions -275T>A, -4549T>C, and -5366G>T.
↵ d Alleles with I399 also included polymorphisms at position I219 and I313.