Engelman CD, Fingerlin TE, Langefeld CD et al.Genetic and environmental determinants of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels in Hispanic and African Americans. J Clin Endocrinol Metab 93:3381-3388

Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, 610 Walnut Street, 1007A WARF, Madison, Wisconsin 53726-2397, USA.
Journal of Clinical Endocrinology & Metabolism (Impact Factor: 6.21). 08/2008; 93(9):3381-8. DOI: 10.1210/jc.2007-2702
Source: PubMed


Vitamin D deficiency is associated with many adverse health outcomes, yet little is known about the genetic epidemiology of vitamin D or its metabolites.
Our objective was to examine the relationship among three vitamin D-related genes and levels of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] in Hispanics (HAs) and African Americans (AAs).
The cross-sectional Insulin Resistance Atherosclerosis Family Study recruited and examined subjects in: Los Angeles, California (AAs; 513 individuals from 42 families); San Luis Valley (SLV), Colorado (HAs; 513 individuals from 30 families); and San Antonio (SA), Texas (HAs; 504 individuals from 58 families).
Plasma levels of 25(OH)D and 1,25(OH)2D were measured.
Levels of 25(OH)D were highest in SLV-HAs [18.3 +/- 7.7 ng/ml (45.7 +/- 19.2 nmol/liter)], lower in SA-HAs [14.6 +/- 6.4 ng/ml (36.4 +/- 16.0 nmol/liter)], and lowest in AAs [11.0 +/- 5.4 ng/ml (27.5 +/- 13.5 nmol/liter)]. Levels of 1,25(OH)2D were similar in AAs [43.5 +/- 13.9 pg/ml (113.1 +/- 36.1 pmol/liter)] and SLV-HAs [43.2 +/- 13.3 pg/ml (112.3 +/- 34.6 pmol/liter)], but higher in SA-HAs [48.6 +/- 17.0 pg/ml (126.4 +/- 44.2 pmol/liter)]. After adjusting for gender and age within the site, two single nucleotide polymorphisms (SNPs) in the vitamin D binding protein gene (DBP), rs4588 and rs7041, were associated with 25(OH)D, and one SNP in the DBP, rs4588, was associated with 1,25(OH)2D at all three study centers.
SNPs in the DBP are associated with levels of 25(OH)D and 1,25(OH)2D in HA and AA participants in the Insulin Resistance Atherosclerosis Family Study.

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Available from: Donald W Bowden, Aug 04, 2014
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    • "On the other hand, in AAs, studies have shown that genetic ancestry contributes to serum 25(OH)D variation (Signorello et al. 2010; Yao et al. 2012), but the association of the GWAS-identified SNPs with serum 25(OH)D levels has not been fully explored. Only a few GWAS-identified variants, located in GC, show significant association with serum 25(OH)D levels in AAs (Engelman et al. 2008; Powe et al. 2013; Signorello et al. 2011). Here, we investigated if 39 SNPs in eight vitamin D pathway genes were associated with serum 25(OH)D concentrations in AAs and EAs. "
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    ABSTRACT: Vitamin D deficiency is more common among African Americans (AAs) than among European Americans (EAs), and epidemiologic evidence links vitamin D status to many health outcomes. Two genome-wide association studies (GWAS) in European populations identified vitamin D pathway gene single-nucleotide polymorphisms (SNPs) associated with serum vitamin D [25(OH)D] levels, but a few of these SNPs have been replicated in AAs. Here, we investigated the associations of 39 SNPs in vitamin D pathway genes, including 19 GWAS-identified SNPs, with serum 25(OH)D concentrations in 652 AAs and 405 EAs. Linear and logistic regression analyses were performed adjusting for relevant environmental and biological factors. The pattern of SNP associations was distinct between AAs and EAs. In AAs, six GWAS-identified SNPs in GC, CYP2R1, and DHCR7/NADSYN1 were replicated, while nine GWAS SNPs in GC and CYP2R1 were replicated in EAs. A CYP2R1 SNP, rs12794714, exhibited the strongest signal of association in AAs. In EAs, however, a different CYP2R1 SNP, rs1993116, was the most strongly associated. Our models, which take into account genetic and environmental variables, accounted for 20 and 28 % of the variance in serum vitamin D levels in AAs and EAs, respectively. Electronic supplementary material The online version of this article (doi:10.1007/s00439-014-1472-y) contains supplementary material, which is available to authorized users.
    Full-text · Article · Aug 2014 · Human Genetics
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    • "The vitamin D binding protein (DBP) is another major determinant to the free and total circulating 25(OH)D concentration [46]; it binds 85–90% of the 25(OH)D in circulation [47], increases the half-life of 25(OH)D as a vitamin D reservoir in circulation, and aids in reabsorbing vitamin D filtered in the kidney [48] [49]. The race-and genetic-dependent variations in the DBP [50] [51] center around 2 single nucleotide polymorphisms (SNPs) in the globulincomplex (Gc) gene [52] that have different affinities for binding 25(OH)D [53]. Thus, certain variants of the DBP may prolong the half-life of vitamin D in circulation more than others [54] and play a role in preventing vitamin D deficiency [55]. "

    Full-text · Article · Aug 2014 · Journal of Clinical and Translational Endocrinology
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    • "The high prevalence of GC1F in blacks results in concentrations of bioavailable 25(OH)D similar to those in whites [5]. Engelman et al. [16] showed that homozygosity for the CG1F allele (DDTT) occurred in 53% of African Americans but only 6% of Caucasians and 13% of Hispanics. The rs4588 and rs7041 SNPs were associated with 25(OH)D levels in Hispanics and African Americans. "
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    ABSTRACT: There is a high prevalence of vitamin D deficiency worldwide, but how to define vitamin D deficiency is controversial. Currently, the plasma concentration of total 25-hydroxyvitamin D [25(OH)D] is considered an indicator of vitamin D status. The free hormone hypothesis states that protein-bound hormones are inactive while unbound hormones are free to exert biological activity. The majority of circulating 25(OH)D and 1,25(OH)2D is tightly bound to vitamin D binding protein (DBP), 10-15% is bound to albumin, and less than 1% of circulating vitamin D exists in an unbound form. While DBP is relatively stable in most healthy populations, a recent study showed that there are gene polymorphisms associated with race and ethnicity that could alter DBP levels and binding affinity. Furthermore, in some clinical situations, total vitamin D levels are altered and knowing whether DBP is also altered may have treatment implications. The aim of this review is to assess DBP concentration in different physiological and pathophysiological conditions. We suggest that DBP should be considered in the interpretation of 25(OH)D levels.
    Full-text · Article · Apr 2014 · International Journal of Endocrinology
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