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Biochemical, Molecular, and Genetic Mechanisms

UGT1A1 Polymorphism Is Associated with Serum Bilirubin Concentrations in a Randomized, Controlled, Fruit and Vegetable Feeding Trial¹

² Interdisciplinary Graduate Program in Nutritional Sciences, Department of Epidemiology, University of Washington, Seattle, WA 98195 and ³ Fred Hutchinson Cancer Research Center, Seattle, WA 98109

^* To whom correspondence should be addressed. E-mail: jlampe{at}fhcrc.org.

UDP-glucuronosyltransferase (UGT) 1A1 glucuronidates bilirubin, estrogens, and exogenous compounds, including dietary carcinogens. The UGT1A1*28 polymorphism, characterized by variation in the number of thymine-adenine repeats in the promoter region, modulates UGT1A1 transcription. Observational and in vitro studies suggest that certain phytochemicals may increase UGT activity. We investigated, in a randomized, controlled, crossover feeding trial, whether 10 servings/d (doses adjusted for body weight) of crucifers, soy, and citrus for 2 wk compared with a fruit- and vegetable-free basal diet affected UGT1A1 activity as measured by serum bilirubin concentrations and whether effects were modulated by the UGT1A1*28 polymorphism. Healthy men (n = 32) and women (n = 31), aged 20–40 y, enrolled based on UGT1A1 genotype, completed the study. We measured bilirubin in blood collected at d 8 and d 15 of each feeding period. Overall, fruit and vegetables (F&V) did not affect serum bilirubin; however, among 7/7 individuals, d 8 total (P = 0.057) and indirect (unconjugated) (P = 0.051) bilirubin tended to be lower when individuals consumed the F&V diet (28.97 ± 2.36 µmol/L and 25.97 ± 2.15 µmol/L) compared with the basal diet (32.46 ± 2.63 µmol/L and 29.31 ± 2.43 µmol/L). We no longer detected this difference at d 15, by which time bilirubin had also decreased when participants consumed the basal diet. Additionally, intervention effects on bilirubin were restricted to women with 7/7 genotype (P = 0.002). These results suggest that serum bilirubin glucuronidation is modulated by dietary intervention, but factors such as UGT1A1 genotype and sex may affect the response to diet.

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