title: UGT1A1 polymorphism is associated with serum bilirubin concentrations in a randomized, controlled, fruit and vegetable feeding trial.
abstract: 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 approximately 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 micromol/L and 25.97 +/- 2.15 micromol/L) compared with the basal diet (32.46 +/- 2.63 micromol/L and 29.31 +/- 2.43 micromol/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.
authors: Interdisciplinary Graduate Program in Nutritional Sciences, Department of Epidemiology, University of Washington, Seattle, WA 98195, USA.
authors: Jyh-Lurn
authors: JL
authors: Chang
authors: Jeannette
authors: J
authors: Bigler
authors: Yvonne
authors: Y
authors: Schwarz
authors: Shuying S
authors: SS
authors: Li
authors: Lin
authors: L
authors: Li
authors: Irena B
authors: IB
authors: King
authors: John D
authors: JD
authors: Potter
authors: Johanna W
authors: JW
authors: Lampe
mesh_terms: D000328:Adult; D001663:Bilirubin / Q000097:blood*; D018592:Cross-Over Studies; D004032:Diet; D005260:Female; D005638:Fruit; D005838:Genotype; D020719:Glucuronides / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D008297:Male; D009994:Osmolar Concentration; D011110:Polymorphism, Genetic; D013997:Time Factors; D014675:Vegetables; D000099148:UGT1A1 Enzyme
chemical_list: D001663:Bilirubin; D020719:Glucuronides; D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme