Blood Vitamin D Levels in Relation to Genetic Estimation of African Ancestry

1International Epidemiology Institute, Rockville, Maryland 20850, USA.
Cancer Epidemiology Biomarkers & Prevention (Impact Factor: 4.13). 09/2010; 19(9):2325-31. DOI: 10.1158/1055-9965.EPI-10-0482
Source: PubMed


African-Americans generally have lower circulating levels of 25 hydroxyvitamin D [25(OH)D] than Whites, attributed to skin pigmentation and dietary habits. Little is known about the genetic determinants of 25(OH)D levels nor whether the degree of African ancestry associates with circulating 25(OH)D.
With the use of a panel of 276 ancestry informative genetic markers, we estimated African and European admixture for a sample of 758 African-American and non-Hispanic White Southern Community Cohort Study participants. For African-Americans, cut points of <85%, 85% to 95%, and >or=95% defined low, medium, and high African ancestry, respectively. We estimated the association between African ancestry and 25(OH)D and also explored whether vitamin D exposure (sunlight, diet) had varying effects on 25(OH)D levels dependent on ancestry level.
The mean serum 25(OH)D levels among Whites and among African-Americans of low, medium, and high African ancestry were 27.2, 19.5, 18.3, and 16.5 ng/mL, respectively. Serum 25(OH)D was estimated to decrease by 1.0 to 1.1 ng/mL per 10% increase in African ancestry. The effect of high vitamin D exposure from sunlight and diet was 46% lower among African-Americans with high African ancestry than among those with low/medium ancestry.
We found novel evidence that the level of African ancestry may play a role in clinical vitamin D status.
This is the first study to describe how 25(OH)D levels vary in relation to genetic estimation of African ancestry. Further study is warranted to replicate these findings and uncover the potential pathways involved.

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    • "Smaller scale replication and candidate gene studies in European and Asian populations also demonstrated the association of variants in these gene regions with serum 25(OH)D levels (Bu et al. 2010; Cooper et al. 2011; Engelman et al. 2013; Lu et al. 2012; Zhang et al. 2012). 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). "
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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.
    Human Genetics 08/2014; 133(11). DOI:10.1007/s00439-014-1472-y · 4.82 Impact Factor
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    • "Molecular genetic data have demonstrated that skin color is under strong recent selection by two separate pathways in Europe and Asia, presumably as a response to ultraviolet B (UVB) exposure (Pilz and others 2009; Reis and others 2005; Wang and others 2008). It has been suggested on the basis of admixture analysis that genes other than those influencing skin color might account in part for lower 25(OH)D in AA (Signorello and others 2010); the data presented here would suggest that these variants play at most a minor role. Thus, while 25(OH)D levels are low in US blacks, in West Africans they are similar to US whites, and these levels are presumably the current best estimate of the " norm " , if not " normal " , for human populations. "
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    ABSTRACT: African Americans (AA) have substantially lower levels of circulating 25-hydroxyvitamin D (25(OH)D) than whites. We compared population-based samples of 25(OH)D in women of African descent from Nigeria and metropolitan Chicago. One hundred women of Yoruba ethnicity from southwest Nigeria and 94 African American women from metropolitan Chicago were recruited and compared using a standardized survey protocol and the same laboratory assay for 25(OH)D. Mean 25(OH)D levels were 64 nmol/l among the Nigerians and 29 nmol/l among the AA. Only 10% of the values were shared in common between the groups, and 76% of the Nigerians were above the currently defined threshold for adequate circulating 25(OH)D compared to 5% of the AA. Modest associations were seen between 25(OH)D and measures of obesity, although adjustment for these traits did not materially affect the group differences. These data support the presumption that skin color is an adaptive trait which has evolved in part to regulate 25(OH)D. It remains undetermined, however, whether lower values observed in AA have negative health consequences. Am. J. Hum. Biol. 25:560–562, 2013.
    American Journal of Human Biology 07/2013; 25(4). DOI:10.1002/ajhb.22395 · 1.70 Impact Factor
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    • "The finding of an inverse association between African ancestry estimated by AIMs and blood 25OHD levels is consistent with a recent community cohort study of AA men and women [33]. Our findings of extensive racial differences in allele frequencies and LD patterns for SNPs in VDR and CYP24A1 are also consistent with those from an earlier study [12]. "
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    ABSTRACT: American women of African ancestry (AA) are more likely than European Americans (EA) to have estrogen receptor (ER)-negative breast cancer. 25-hydroxyvitamin D (25OHD) is low in AAs, and was associated with ER-negative tumors in EAs. We hypothesized that racial differences in 25OHD levels, as well as in inherited genetic variations, may contribute, in part, to the differences in tumor characteristics. In a case (n = 928)-control (n = 843) study of breast cancer in AA and EA women, we measured serum 25OHD levels in controls and tested associations between risk and tag single nucleotide polymorphisms (SNPs) in VDR, CYP24A1 and CYP27B1, particularly by ER status. More AAs had severe vitamin D deficiency (< 10 ng/ml) than EAs (34.3% vs 5.9%), with lowest levels among those with the highest African ancestry. Associations for SNPs differed by race. Among AAs, VDR SNP rs2239186, associated with higher serum levels of 25OHD, decreased risk after correction for multiple testing (OR = 0.53, 95% CI = 0.31-0.79, p by permutation = 0.03), but had no effect in EAs. The majority of associations were for ER-negative breast cancer, with seven differential associations between AA and EA women for CYP24A1 (p for interaction < 0.10). SNP rs27622941 was associated with a > twofold increased risk of ER-negative breast cancer among AAs (OR = 2.62, 95% CI = 1.38-4.98), but had no effect in EAs. rs2209314 decreased risk among EAs (OR = 0.38, 95% CI = 0.20-0.73), with no associations in AAs. The increased risk of ER-negative breast cancer in AAs compared to EAs was reduced and became non-significant (OR = 1.20, 95% CI = 0.80-1.79) after adjusting for these two CYP24A1 SNPs. These data suggest that genetic variants in the vitamin D pathway may be related to the higher prevalence of ER-negative breast cancer in AA women.
    Breast cancer research: BCR 04/2012; 14(2):R58. DOI:10.1186/bcr3162 · 5.49 Impact Factor
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