ABSTRACT
Cardiovascular risk increases in women after menopause. Unfavorable lipid-lipoprotein changes due to a lack of estrogens may have an important role in this context. Estrogen actions are mainly mediated by their binding to two estrogen receptors (ERs) whose signaling may be conditioned by different factors. Calcium, vitamin D, and genistein, among others, cause a beneficial effect on serum lipid profile by its modulation. Some genetic factors can also determine this signal. We determined the possible additive effect of genistein on calcium and vitamin D supplementation regarding serum lipid profile changes and whether ER polymorphisms may mediate in this effect. We performed a prospective, double blind study in which women were randomized in two groups: one group received calcium and vitamin D and the other group received calcium, vitamin D and genistein. Subsequently, we studied rs9340799, rs928554, and rs4986938 ER polymorphisms in both groups. Our results showed that being a carrier of the variant allele G of rs928554 polymorphism was associated with a greater decrease in triglyceride levels and that the homozygous AA genotype of rs9340799 polymorphism was associated with a greater decrease in total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels after calcium, vitamin D, and genistein supplementation. This is the first report showing an association between polymorphisms in ER genes and an improvement of the serum lipid profile after taking calcium, vitamin D, and genistein supplementation in postmenopausal women. It reinforces the hypothesis that genetic factors are crucial in ER signalling.
Subject(s)
Calcium/pharmacology , Genistein/pharmacology , Polymorphism, Genetic/genetics , Postmenopause/blood , Vitamin D/pharmacology , Adult , Double-Blind Method , Female , Genotype , Humans , Middle Aged , Prospective Studies , Receptors, Estrogen/genetics , Receptors, Estrogen/metabolismABSTRACT
AIMS: The objective of this study was to determine whether vitamin D and genistein supplementation had an additive beneficial effect on levels of vitamin D and bone markers and whether this effect was mediated by genes regulating isoflavone metabolism. MATERIALS AND METHODS: We carried out a prospective study in postmenopausal women randomized to calcium and vitamin D supplementation or calcium, vitamin D, and genistein supplementation. Vitamin D, parathyroid hormone (PTH), cross-linked C-telopeptide (CTX), and procollagen 1 N-terminal (P1NP) were determined by electrochemiluminescence. Three SNPs - rs2231142 (ABCG2), rs358231 (cytosolic ß-glucosidase [CBG]), and rs2273697 (ABCC2) - were determined. RESULTS: We included 102 women. The effects on bone remodeling were similar: rises in vitamin D were significantly associated with reductions in PTH, CTX, and P1NP. Pharmacogenomic analysis of the genotypes showed that, in AT heterozygotes of the CBG1368T>A polymorphism, CTX and P1NP were not reduced. CONCLUSION: Genistein added to calcium and vitamin D supplementation had no additional effect. The supplementation of individual AT heterozygotes of the CBG1368T>A polymorphism had no effect on markers of bone remodeling.
Subject(s)
Bone Remodeling/drug effects , Genistein/administration & dosage , Isoflavones/metabolism , Vitamin D/blood , ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics , Biomarkers/blood , Calcium, Dietary/administration & dosage , Collagen Type I/blood , Dietary Supplements , Female , Genistein/metabolism , Genotype , Healthy Volunteers , Humans , Middle Aged , Multidrug Resistance-Associated Protein 2 , Multidrug Resistance-Associated Proteins/genetics , Neoplasm Proteins/genetics , Nutrigenomics , Parathyroid Hormone/blood , Peptide Fragments/blood , Peptides/blood , Polymorphism, Single Nucleotide , Postmenopause , Procollagen/blood , Prospective Studies , Seasons , Vitamin D/administration & dosage , beta-Glucosidase/geneticsABSTRACT
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