TABLE 2

UGT1A1 and UGT1A9 protein expression and glucuronosyltransferase activities in human livers genotyped for functional polymorphisms

Data are expressed as mean ± S.D.


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.