title: Genetic variants and non-genetic factors predict circulating vitamin D levels in Hispanic and non-Hispanic White women: the Breast Cancer Health Disparities Study.
abstract: Genome-wide association studies (GWAS) have identified common polymorphisms in or near GC, CYP2R1, CYP24A1, and NADSYN1/DHCR7 genes to be associated with circulating levels of 25-hydroxyvitamin D [25(OH)D] in European populations. To replicate these GWAS findings, we examined six selected polymorphisms from these regions and their relation with circulating 25(OH)D levels in 1,605 Hispanic women (629 U.S. Hispanics and 976 Mexicans) and 354 non-Hispanic White (NHW) women. We also assessed the potential interactions between these variants and known non-genetic predictors of 25(OH)D levels, including body mass index (BMI), sunlight exposure and vitamin D intake from diet and supplements. The minor alleles of the two GC polymorphisms (rs7041 and rs2282679) were significantly associated with lower 25(OH)D levels in both Hispanic and NHW women. The CYP2R1 polymorphism, rs2060793, also was significantly associated with 25(OH)D levels in both groups. We found no significant associations for the polymorphisms in the CYP24A1. In Hispanic controls, 25(OH)D levels were significantly associated with the rs12785878T and rs1790349G haplotype in the NADSYN1/DHCR7 region. Significant interactions between GC rs2282679 and BMI and between rs12785878 and time spent in outdoor activities were observed. These results provide further support for the contribution of common genetic variants to individual variability in circulating 25(OH)D levels. The observed interactions between SNPs and non-genetic factors warrant confirmation.
authors.affiliation: Cancer Prevention Institute of California Fremont, CA 94538, USA ; Biomedical Informatics Training Program, Stanford University Stanford, CA 94305, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California Los Angeles, CA 90089, USA ; Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California Los Angeles, CA 90033, USA.
authors.forename: Sue Ann
authors.initials: SA
authors.lastname: Ingles
authors.affiliation: Instituto Nacional de Salud Pública Cuernavaca Morelos CP 62100, México.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Torres-Mejía
authors.affiliation: Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California Los Angeles, CA 90089, USA.
authors.forename: Mariana C
authors.initials: MC
authors.lastname: Stern
authors.affiliation: Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California Los Angeles, CA 90033, USA.
authors.forename: Frank Z
authors.initials: FZ
authors.lastname: Stanczyk
authors.affiliation: Department of Cancer Biology, School of Medicine, Wake Forest University Medical Center Boulevard, Winston-Salem, NC 27157, USA.
authors.forename: Gary G
authors.initials: GG
authors.lastname: Schwartz
authors.affiliation: Cancer Prevention Institute of California Fremont, CA 94538, USA.
authors.forename: David O
authors.initials: DO
authors.lastname: Nelson
authors.affiliation: Division of General Internal Medicine, Department of Medicine,Institute for Human Genetics and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, CA 94158, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Fejerman
authors.affiliation: Department of Medicine, University of Utah Salt Lake City, UT 84132, USA.
authors.forename: Roger K
authors.initials: RK
authors.lastname: Wolff
authors.affiliation: Department of Medicine, University of Utah Salt Lake City, UT 84132, USA.
authors.forename: Martha L
authors.initials: ML
authors.lastname: Slattery
authors.affiliation: Cancer Prevention Institute of California Fremont, CA 94538, USA ; Division of Epidemiology, Department of Health Research and Policy, Stanford Cancer Institute, Stanford University School of Medicine Stanford, CA 94503, USA.
authors.forename: Esther M
authors.initials: EM
authors.lastname: John
keywords: Circulating levels; Hispanics; SNPs; genetic polymorphisms; genotype-phenotype correlation; vitamin D