title: Polymorphisms in genes involved in the metabolism and transport of soy isoflavones affect the urinary metabolite profile in premenopausal women following consumption of a commercial soy supplement as a single bolus dose.
abstract: METHODS
  Genetic variation in relevant enzymes and transporters may contribute to discordant observations concerning health outcomes of dietary isoflavone consumption, so we examined the association of the UGT1A1*28 promoter polymorphism and of other SNPs with isoflavone metabolites in urine.
  
  
  RESULTS
  We genotyped prospectively for polymorphisms in UGT1A1 (UGT1A1*28), LPH (666G>A), CBG (1368T>A), ABCG2 (421C>A), and ABCC2 (1249G>A) to select 100 women (18-50 years) to receive a commercial soy supplement as a single dose and collect all urine over 24 h for analysis by RP-HPLC. We observed large differences in isoflavone recovery (mean 39%, eightfold variation) and metabolites. Glucuronides were the major metabolites (72% of total). UGT1A1*28 was associated only with percentage of glycitein as sulphate (positive; p = 0.046), but excluding five participants with both minor alleles of CBG and ABCG2 uncovered additional associations with percentage of glycitein as glucuronide (negative; p = 0.028), combined isoflavones as sulphate (positive; p = 0.035) and sulphate-to-glucuronide ratio for combined isoflavones (positive; p = 0.036). CBG1368T>A, ABCG2 421C>A, and ABCC2 1249G>A were also associated with differences in isoflavone metabolites in urine.
  
  
  CONCLUSIONS
  Genetic variation in UGT1A1, CBG, ABCG2, and ABCC2 influences isoflavone metabolism so may affect benefits of dietary consumption.
authors.affiliation: Institute for Cell and Molecular Biosciences, Human Nutrition Research Centre, Newcastle University, Medical School, Newcastle upon Tyne, UK.
authors.forename: Luisa A
authors.initials: LA
authors.lastname: Wakeling
authors.forename: Dianne
authors.initials: D
authors.lastname: Ford
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D002851:Chromatography, High Pressure Liquid; D004032:Diet; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D020719:Glucuronides / Q000378:metabolism / Q000652:urine; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007529:Isoflavones / Q000378:metabolism* / Q000652:urine*; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D011110:Polymorphism, Genetic; D017697:Premenopause / Q000378:metabolism* / Q000652:urine; D011446:Prospective Studies; D045730:Soy Foods / Q000032:analysis*; D044465:White People; D055815:Young Adult; D000099148:UGT1A1 Enzyme
chemical_list: D020719:Glucuronides; D014453:Glucuronosyltransferase; D007529:Isoflavones; D000089762:Multidrug Resistance-Associated Protein 2; D000099148:UGT1A1 Enzyme; C000715087:ABCC2 protein, human