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

被引:40
作者
Elnenaei, Manal O. [1 ]
Chandra, Rama [1 ]
Mangion, Tina [1 ]
Moniz, Caje [1 ]
机构
[1] Kings Coll Hosp London, Dept Clin Biochem, London SE5 9RS, England
关键词
Vitamin D receptor; Oestrogen receptor; Genotyping; Metabolomics; BONE-MINERAL DENSITY; D-RECEPTOR GENOTYPES; OSTEOPOROTIC FRACTURES; ESTROGEN; GENE; ABSORPTION; POLYMORPHISMS; NUTRIGENOMICS;
D O I
10.1017/S0007114510003065
中图分类号
R15 [营养卫生、食品卫生]; TS201 [基础科学];
学科分类号
100403 ;
摘要
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.
引用
收藏
页码:71 / 79
页数:9
相关论文
共 40 条
[11]   VITAMIN-D-RECEPTOR GENOTYPES IN PRIMARY HYPERPARATHYROIDISM [J].
CARLING, T ;
KINDMARK, A ;
HELLMAN, P ;
LUNDGREN, E ;
LJUNGHALL, S ;
RASTAD, J ;
AKERSTROM, G ;
MELHUS, H .
NATURE MEDICINE, 1995, 1 (12) :1309-1311
[12]   Interaction between vitamin D receptor genotype and estrogen receptor α genotype influences vertebral fracture risk [J].
Colin, EM ;
Uitterlinden, AG ;
Meurs, JBJ ;
Bergink, AP ;
van de Klift, M ;
Fang, Y ;
Arp, PP ;
Hofman, A ;
van Leeuwen, JPTM ;
Pols, HAP .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2003, 88 (08) :3777-3784
[13]  
Cross HS, 2009, ANTICANCER RES, V29, P3705
[14]   Epidemiology and outcomes of osteoporotic fractures [J].
Cummings, SR ;
Melton, LJ .
LANCET, 2002, 359 (9319) :1761-1767
[15]   Impact of genetic variation on metabolic response of bone to diet [J].
Cusack, S ;
Cashman, KD .
PROCEEDINGS OF THE NUTRITION SOCIETY, 2003, 62 (04) :901-912
[16]   CALCIUM-ABSORPTION ON HIGH AND LOW-CALCIUM INTAKES IN RELATION TO VITAMIN-D-RECEPTOR GENOTYPE [J].
DAWSONHUGHES, B ;
HARRIS, SS ;
FINNERAN, S .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1995, 80 (12) :3657-3661
[17]   Current limitations of SNP data from the public domain for studies of complex disorders: a test for ten candidate genes for obesity and osteoporosis [J].
Dvornyk, V ;
Long, JR ;
Xiong, DH ;
Liu, PY ;
Zhao, LJ ;
Shen, H ;
Zhang, YY ;
Liu, YJ ;
Rocha-Sanchez, S ;
Xiao, P ;
Recker, RR ;
Deng, HW .
BMC GENETICS, 2004, 5 (1)
[18]  
Ferrari Serge L., 2005, Molecular Aspects of Medicine, V26, P145, DOI 10.1016/j.mam.2005.01.002
[19]   Can the WHO criteria for diagnosing osteoporosis be applied to calcaneal quantitative ultrasound? [J].
Frost, ML ;
Blake, GM ;
Fogelman, I .
OSTEOPOROSIS INTERNATIONAL, 2000, 11 (04) :321-330
[20]   Vitamin D receptor genotypes and intestinal calcium absorption in postmenopausal women [J].
Gennari, L ;
Becherini, L ;
Masi, L ;
Gonnelli, S ;
Cepollaro, C ;
Martini, S ;
Mansani, R ;
Brandi, ML .
CALCIFIED TISSUE INTERNATIONAL, 1997, 61 (06) :460-463