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Vitamin D binding protein genotype is associated with plasma 25OHD concentration in West African children.
Bone. 2015 May; 74:166-70.BONE

Abstract

Vitamin D is well known for its role in promoting skeletal health. Vitamin D status is determined conventionally by circulating 25-dihydroxyvitamin D (25OHD) concentration. There is evidence indicating that circulating 25OHD concentration is affected by variation in Gc, the gene encoding the vitamin D binding protein (DBP). The composite genotype of two single nucleotide polymorphisms (rs7041 and rs4588) results in different DBP isotypes (Gc1f, Gc1s and Gc2). The protein configurational differences among DBP isotypes affect DBP substrate binding affinity. The aims of this study were to determine 1) Gc variant frequencies in a population from an isolated rural region of The Gambia, West Africa (n=3129) with year-round opportunity for cutaneous vitamin D synthesis and 2) the effects of Gc variants on 25OHD concentration (n=237) in a genetically representative sub-group of children (mean (SD) age: 11.9 (4.8) years). The distribution of Gc variants was Gc1f: 0.86, Gc1s: 0.11 and Gc2: 0.03. The mean (SD) concentration of 25OHD was 59.6 (12.9) nmol/L and was significantly higher in those homozygous for Gc1f compared to other Gc variants (60.7 (13.1) vs. 56.6 (12.1) nmol/L, P=0.03). Plasma 25OHD and 1,25(OH)2D concentration was significantly associated with parathyroid hormone in Gc1f-1f but not in the other Gc variants combined. This study demonstrates that different Gc variants are associated with different 25OHD concentrations in a rural Gambian population. Gc1f-1f, thought to have the highest affinity for 25OHD, had the highest 25OHD concentration compared with lower affinity Gc variants. The considerable difference in Gc1f frequency observed in Gambians compared with other non-West African populations and associated differences in plasma 25OHD concentration, may have implications for the way in which vitamin D status should be interpreted across different ancestral groups.

Authors+Show Affiliations

MRC Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge CB1 9NL, UK. Electronic address: vickie.braithwaite@mrc-hnr.cam.ac.uk.MRC Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge CB1 9NL, UK.MRC Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge CB1 9NL, UK.MRC International Nutrition Group at London School of Hygiene & Tropical Medicine, Keppel St, London WC1E 7HT UK and MRC Unit, The Gambia.MRC Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge CB1 9NL, UK; MRC Keneba, Keneba, The Gambia.MRC International Nutrition Group at London School of Hygiene & Tropical Medicine, Keppel St, London WC1E 7HT UK and MRC Unit, The Gambia.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25652210

Citation

Braithwaite, V S., et al. "Vitamin D Binding Protein Genotype Is Associated With Plasma 25OHD Concentration in West African Children." Bone, vol. 74, 2015, pp. 166-70.
Braithwaite VS, Jones KS, Schoenmakers I, et al. Vitamin D binding protein genotype is associated with plasma 25OHD concentration in West African children. Bone. 2015;74:166-70.
Braithwaite, V. S., Jones, K. S., Schoenmakers, I., Silver, M., Prentice, A., & Hennig, B. J. (2015). Vitamin D binding protein genotype is associated with plasma 25OHD concentration in West African children. Bone, 74, 166-70. https://doi.org/10.1016/j.bone.2014.12.068
Braithwaite VS, et al. Vitamin D Binding Protein Genotype Is Associated With Plasma 25OHD Concentration in West African Children. Bone. 2015;74:166-70. PubMed PMID: 25652210.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vitamin D binding protein genotype is associated with plasma 25OHD concentration in West African children. AU - Braithwaite,V S, AU - Jones,K S, AU - Schoenmakers,I, AU - Silver,M, AU - Prentice,A, AU - Hennig,B J, Y1 - 2015/01/31/ PY - 2014/10/20/received PY - 2014/12/09/revised PY - 2014/12/15/accepted PY - 2015/2/6/entrez PY - 2015/2/6/pubmed PY - 2015/12/15/medline KW - 25OHD KW - Africa KW - DBP KW - Gc genotype KW - Vitamin D SP - 166 EP - 70 JF - Bone JO - Bone VL - 74 N2 - Vitamin D is well known for its role in promoting skeletal health. Vitamin D status is determined conventionally by circulating 25-dihydroxyvitamin D (25OHD) concentration. There is evidence indicating that circulating 25OHD concentration is affected by variation in Gc, the gene encoding the vitamin D binding protein (DBP). The composite genotype of two single nucleotide polymorphisms (rs7041 and rs4588) results in different DBP isotypes (Gc1f, Gc1s and Gc2). The protein configurational differences among DBP isotypes affect DBP substrate binding affinity. The aims of this study were to determine 1) Gc variant frequencies in a population from an isolated rural region of The Gambia, West Africa (n=3129) with year-round opportunity for cutaneous vitamin D synthesis and 2) the effects of Gc variants on 25OHD concentration (n=237) in a genetically representative sub-group of children (mean (SD) age: 11.9 (4.8) years). The distribution of Gc variants was Gc1f: 0.86, Gc1s: 0.11 and Gc2: 0.03. The mean (SD) concentration of 25OHD was 59.6 (12.9) nmol/L and was significantly higher in those homozygous for Gc1f compared to other Gc variants (60.7 (13.1) vs. 56.6 (12.1) nmol/L, P=0.03). Plasma 25OHD and 1,25(OH)2D concentration was significantly associated with parathyroid hormone in Gc1f-1f but not in the other Gc variants combined. This study demonstrates that different Gc variants are associated with different 25OHD concentrations in a rural Gambian population. Gc1f-1f, thought to have the highest affinity for 25OHD, had the highest 25OHD concentration compared with lower affinity Gc variants. The considerable difference in Gc1f frequency observed in Gambians compared with other non-West African populations and associated differences in plasma 25OHD concentration, may have implications for the way in which vitamin D status should be interpreted across different ancestral groups. SN - 1873-2763 UR - https://www.unboundmedicine.com/medline/citation/25652210/Vitamin_D_binding_protein_genotype_is_associated_with_plasma_25OHD_concentration_in_West_African_children_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S8756-3282(15)00027-7 DB - PRIME DP - Unbound Medicine ER -