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Common vitamin D pathway gene variants reveal contrasting effects on serum vitamin D levels in African Americans and European Americans |
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| Authors: | Ken Batai Adam B Murphy Ebony Shah Maria Ruden Jennifer Newsome Sara Agate Michael A Dixon Hua Yun Chen Leslie A Deane Courtney M P Hollowell Chiledum Ahaghotu Rick A Kittles |
| Institution: | 1. Division of Urology, Department of Surgery, University of Arizona College of Medicine, University of Arizona Cancer Center, P.O. Box 245024, 1515 N. Campbell Ave., Tucson, AZ, 85724, USA 2. Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, USA 3. Jesse Brown Veterans Affairs Medical Center, Chicago, USA 4. Department of Medicine, University of Illinois at Chicago, Chicago, USA 5. Center for Clinical and Translational Science, University of Illinois at Chicago, Chicago, USA 6. Division of Health Policy and Administration, School of Public Health, University of Illinois at Chicago, Chicago, USA 7. Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois at Chicago, Chicago, USA 8. Department of Urology, Rush University Medical Center, Chicago, USA 9. Section of Urology, Department of Surgery, Cook County Health and Hospitals System, Chicago, USA 10. Division of Urology, Department of Surgery, Howard University Hospital, Washington, D.C., USA |
| 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. |
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