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

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Abstract
Scope: 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.Methods and 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.Conclusion: Genetic variation in UGT1A1, CBG, ABCG2, and ABCC2 influences isoflavone metabolism so may affect benefits of dietary consumption.
Funding Information
  • UK Biotechnology and Biological Sciences Research Council (BBE0074571)

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