Genomic and metabolomic patterns segregate with responses to calcium and vitamin D supplementation

TY - JOUR

T1 - Genomic and metabolomic patterns segregate with responses to calcium and vitamin D supplementation

AU - Elnenaei, Manal O.

AU - Chandra, Rama

AU - Mangion, Tina

AU - Moniz, Caje

PY - 2011/1/14

Y1 - 2011/1/14

N2 - 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 NAIR 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 Tag1 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.

AB - 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 NAIR 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 Tag1 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.

KW - Vitamin D receptor

KW - Oestrogen receptor

KW - Genotyping

KW - Metabolomics

KW - BONE-MINERAL DENSITY

KW - D-RECEPTOR GENOTYPES

KW - OSTEOPOROTIC FRACTURES

KW - PRIMARY HYPERPARATHYROIDISM

KW - POSTMENOPAUSAL WOMEN

KW - ESTROGEN

KW - POLYMORPHISMS

KW - ABSORPTION

KW - GENE

KW - NUTRIGENOMICS

U2 - 10.1017/S0007114510003065

DO - 10.1017/S0007114510003065

M3 - Article

SN - 0007-1145

VL - 105

SP - 71

EP - 79

JO - British Journal of Nutrition

JF - British Journal of Nutrition

IS - 1

ER -