title: Vitamin D binding protein genotype is associated with plasma 25OHD concentration in West African children.
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: MRC Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge CB1 9NL, UK. Electronic address: vickie.braithwaite@mrc-hnr.cam.ac.uk.
authors: V S
authors: VS
authors: Braithwaite
authors: MRC Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge CB1 9NL, UK.
authors: K S
authors: KS
authors: Jones
authors: MRC Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge CB1 9NL, UK.
authors: I
authors: I
authors: Schoenmakers
authors: MRC International Nutrition Group at London School of Hygiene & Tropical Medicine, Keppel St, London WC1E 7HT UK and MRC Unit, The Gambia.
authors: M
authors: M
authors: Silver
authors: MRC Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge CB1 9NL, UK; MRC Keneba, Keneba, The Gambia.
authors: A
authors: A
authors: Prentice
authors: MRC International Nutrition Group at London School of Hygiene & Tropical Medicine, Keppel St, London WC1E 7HT UK and MRC Unit, The Gambia.
authors: B J
authors: BJ
authors: Hennig
mesh_terms: D002117:Calcitriol / Q000378:metabolism; D002648:Child; D005260:Female; D005714:Gambia; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D010281:Parathyroid Hormone / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014809:Vitamin D-Binding Protein / Q000235:genetics*
chemical_list: D010281:Parathyroid Hormone; D014809:Vitamin D-Binding Protein; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D002117:Calcitriol
keywords: 25OHD; Africa; DBP; Gc genotype; Vitamin D
references: Bone. 2012 Jun;50(6):1351-6
references: 22465847
references: Acta Paediatr. 2009 Aug;98(8):1360-2
references: 19594476
references: Proc Natl Acad Sci U S A. 1990 Jul;87(14):5474-8
references: 2371283
references: J Steroid Biochem. 1980 Sep;13(9):1029-34
references: 6893475
references: Hum Genet. 1993 Sep;92(2):183-8
references: 8370586
references: Acta Pathol Microbiol Scand. 1959;47:169-72
references: 14402001
references: J Nutr. 2008 Dec;138(12):2468-73
references: 19022974
references: Nucleic Acids Res. 1988 Feb 11;16(3):1215
references: 3344216
references: Science. 2002 Jun 21;296(5576):2225-9
references: 12029063
references: Bone Res. 2013;1(1):2-10
references: 25285234
references: Stat Med. 2000 Nov 30;19(22):3109-25
references: 11113946
references: J Clin Endocrinol Metab. 1986 Oct;63(4):954-9
references: 3745408
references: Am J Clin Nutr. 2006 Mar;83(3):657-66
references: 16522914
references: J Steroid Biochem Mol Biol. 2014 Oct;144 Pt A:132-7
references: 24095930
references: Bone. 2012 Jan;50(1):218-25
references: 22023931
references: Br J Nutr. 2012 Apr;107(8):1128-37
references: 21896243
references: Hum Genet. 1986 Jul;73(3):225-9
references: 3015768
references: J Steroid Biochem. 1989 Jan;32(1A):59-63
references: 2913402
references: J Immunol. 1996 Aug 15;157(4):1744-9
references: 8759764
references: J Clin Endocrinol Metab. 2014 Sep;99(9):3373-81
references: 24885631
references: Bioinformatics. 2010 Nov 15;26(22):2867-73
references: 20926424
references: Lancet. 2010 Jul 17;376(9736):180-8
references: 20541252
references: Am J Clin Nutr. 2014 Jun;99(6):1424-31
references: 24740207
references: Hum Genet. 1986 Apr;72(4):281-93
references: 3516862