Table 2.
Alteration in catalytic activity: UGT1A7 polymorphisms (activities in pmol/min/mg)
| Substrate | UGT1A7*1 wild-type | UGT1A7*4 W208R | UGT1A7*2 N129K/R131K | UGT1A7*3 N129K/R131K/W208R |
| 1-Nitrophenol | 1773 (615) | 32 (23) | 13 (2) | nd |
| 1-Naphthol | 592 (100) | 36 (16) | nd | nd |
| 4-Methylumbelliferone | 12110 (361) | 191 (136) | 13 (2) | nd |
| 4-tert-Butylphenol | 121 (2) | nd | 12 (0.2) | nd |
| 7-Hydroxybenzo(α)pyrene | 1263 (20) | 51 (10) | 14 (0.5) | nd |
| 8-Hydroxybenzo(α)pyrene | 98 (6) | nd | 12 (1) | nd |
| 7–8-Hydroxybenzo(α)pyrene | 79 (7) | nd | 15 (1) | nd |
| 9-Hydroxybenzo(α)pyrene | 198 (15) | nd | 16 (3) | nd |
| PhIP | 48 (4) | nd | 17 (5) | nd |
Mean catalytic activities of the missense mutations identified in exon 1 of UGT1A7. The wild-type UGT1A7*1 exhibited high activities with phenolic compounds as well as with benzo(α)pyrene metabolites, as previously characterised.3 The analysis demonstrates reduced glucuronidation activities of the polymorphic UGT1A7 proteins. The major risk allele identified in the patient analysis, UGT1A7*3, exhibited the lowest carcinogen detoxification activity.
PhIP, amino-1-methyl-6-phenylimidazo-(4.5-β)-pyridine (PhIP); nd, not detected.
Values are mean (SD).