title: Genomic and metabolomic patterns segregate with responses to calcium and vitamin D supplementation.
abstract: Inter-individual response differences to vitamin D and Ca supplementation may be under genetic control through vitamin D and oestrogen receptor genes, which may influence their absorption and/or metabolism. Metabolomic studies on blood and urine from subjects supplemented with Ca and vitamin D reveal different metabolic profiles that segregate with genotype. Genotyping was performed for oestrogen receptor 1 gene (ESR1) and vitamin D receptor gene (VDR) in fifty-six postmenopausal women. Thirty-six women were classified as low bone density as determined by a heel ultrasound scan and twenty women had normal bone density acting as 'controls'. Those with low bone density (LBD) were supplemented with oral Ca and vitamin D and were classified according to whether they were 'responders' or 'non-responders' according to biochemical results before and after therapy compared to controls receiving no supplementation. Metabolomic studies on serum and urine were done for the three groups at 0 and 3 months of therapy using NMR spectroscopy with pattern recognition. The 'non-responder' group showed a higher frequency of polymorphisms in the ESR1 (codons 10 and 325) and VDR (Bsm1 and Taq1), compared with to the 'responders'. The wild-type genotype for Fok1 was more frequent in those with LBD (70 %) compared with the control group (10 %). Distinctive patterns of metabolites were displayed by NMR studies at baseline and 3 months of post-treatment, segregating responders from non-responders and controls. Identification of potential 'non-responders' to vitamin D and Ca, before therapy, based on a genomic and/or metabolomic profile would allow targeted selection of optimal therapy on an individual basis.
authors: Clinical Biochemistry Department, King's College Hospital, Denmark Hill, London SE5 9RS, UK.
authors: Manal O
authors: MO
authors: Elnenaei
authors: Rama
authors: R
authors: Chandra
authors: Tina
authors: T
authors: Mangion
authors: Caje
authors: C
authors: Moniz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000235:genetics* / Q000502:physiology; D002136:Calcium, Dietary / Q000008:administration & dosage / Q000378:metabolism*; D016022:Case-Control Studies; D019587:Dietary Supplements; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D016678:Genome; D005838:Genotype; D006801:Humans; D007408:Intestinal Absorption; D009682:Magnetic Resonance Spectroscopy; D055442:Metabolome; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D018167:Receptors, Calcitriol / Q000235:genetics*; D014807:Vitamin D / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*
chemical_list: D002136:Calcium, Dietary; D047628:Estrogen Receptor alpha; D018167:Receptors, Calcitriol; D014807:Vitamin D