Vitamin D Intake and Season Modify the Effects of the GC and CYP2R1 Genes on 25-Hydroxyvitamin D Concentrations1,2,3
J. Nutr. January 1, 2013 jn.112.169482
Corinne D. Engelman4, cengelman at wisc.edu, Kristin J. Meyers5, Sudha K. Iyengar7, Zhe Liu5, Chitra K. Karki5, Robert P. Igo Jr7, Barbara Truitt7, Jennifer Robinson8,9, Gloria E. Sarto6, Robert Wallace9, Barbara A. Blodi5, Michael L. Klein10, Lesley Tinker11, Erin S. LeBlanc12, Rebecca D. Jackson13, Yiqing Song14, JoAnn E. Manson14,15, Julie A. Mares5, and Amy E. Millen16
4 Department of Population Health Sciences
5 Department of Ophthalmology and Visual Sciences, and
6 Department of Obstetrics and Gynecology, University of Wisconsin School of Medicine and Public Health, Madison, WI
7 Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH
8 Department of Medicine, and
9 Department of Epidemiology, University of Iowa, Iowa City, IA
10 Casey Eye Institute, Oregon Health and Science University, Portland, OR
11 Fred Hutchinson Cancer Research Center, Seattle, WA
12 Kaiser Permanente Center for Health Research, Portland, OR
13 Department of Internal Medicine, Ohio State Wexner Medical Center, Columbus, OH
14 Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA
15 Department of Epidemiology, Harvard School of Public Health, Boston, MA; and
16 Department of Social and Preventive Medicine, The State University of New York, Buffalo, NY
Vitamin D deficiency defined by the blood concentration of 25-hydroxyvitamin D [25(OH)D]} has been associated with many adverse health outcomes. Genetic and nongenetic factors account for variation in 25(OH)D, but the role of interactions between these factors is unknown.
To assess this, we examined 1204 women of European descent from the Carotenoids in Age-Related Eye Disease Study, an ancillary study of the Women’s Health Initiative Observational Study. Twenty-nine single nucleotide polymorphisms (SNPs) in 4 genes, GC, CYP2R1, DHCR7, and CYP24A1, from recent meta-analyses of 25(OH)D genome-wide association studies were genotyped.
Associations between these SNPs and 25(OH)D were tested using generalized linear regression under an additive genetic model adjusted for age, blood draw month, and ancestry.
Results were stratified by season of blood draw and, separately, vitamin D intake for the 6 SNPs showing a significant association with 25(OH)D at the P < 0.01 level.
Two nonsynonymous SNPs in GC and 4 SNPs in CYP2R1 were strongly associated with 25(OH)D in individuals whose blood was drawn in summer (P ≤ 0.002) but not winter months and, independently, in individuals with vitamin D intakes ≥400 (P ≤ 0.004) but not <400 IU/d (10 μg/d).
This effect modification, if confirmed, has important implications for the design of genetic studies for all health outcomes and for public health recommendations and clinical practice guidelines regarding the achievement of adequate vitamin D status.
Manuscript received: September 10, 2012; Initial review completed: October 4, 2012.; Revision accepted: October 30, 2012.
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