Cruciferase interact with the UGT1A1*28 polymorphism to determine serum bilirubin levels in humans

UDP-glucuronosyltransferase (UGT) 1A1 is a conjugating biotransformation enzyme that plays a role in maintaining levels of endogenous compounds (e.g., bilirubin) and handling exogenous compounds, including carcinogens. The UGT1A1*28 polymorphism results in decreased UGT1A1 promoter activity due to 7 thymine-adenine (TA) repeats instead of the commonly found 6 repeats. Studies indicate that foods from the botanical families Cruciferae (e.g., broccoli), Rutaceae (citrus), Lillaceae (e.g., onions), and Leguminosae (legumes) may increase UGT activity. We investigated, in an observational study, whether foods from these botanical groups were associated with increased UGT1A1 activity as indicated by serum bilirubin concentrations and whether the effect varied by UGT1A1*28 genotype, comparing those homozygous for the [TA] ₇-repeat allele (7/7) to homozygous wild-types (6/6) and heterozygotes (6/7) combined. Healthy volunteers completed 3-d food records. Blood samples were drawn for genomic DNA collection and bilirubin measures. For total, direct, and indirect bilirubin measures, there was no significant association with any botanical group independently. There was a significant inverse association between all 3 bilirubin measures and interaction of UGT1A1*28 genotype with Cruciferae intake (P < 0.02 for each measure); individuals with the 7/7 genotype had reduced bilirubin concentrations with increased intake of cruciferous vegetables, whereas individuals with the 6/6 or 6/7 genotype did not. With regard to UGT1A1-conjugated carcinogens (e.g., heterocyclic amines, polycyclic aromatic hydrocarbons), individuals with decreased UGT1A1 activity due to the 7/7 genotype may be at greater risk for carcinogenesis, but our results imply that they also may have greater opportunity to decrease that risk through dietary intervention.