Vitamin D intake and season modify the effects of the GC and CYP2R1 genes on 25-hydroxyvitamin D concentrations

Corinne D. Engelman, Kristin J. Meyers, Sudha K. Iyengar, Zhe Liu, Chitra K. Karki, Robert P. Igo, Barbara Truitt, Jennifer Robinson, Gloria E. Sarto, Robert Wallace, Barbara A. Blodi, Michael L. Klein, Lesley Tinker, Erin S. LeBlanc, Rebecca D. Jackson, Yiqing Song, Joann E. Manson, Julie A. Mares, Amy E. Millen

Research output: Contribution to journalReview article

43 Citations (Scopus)

Abstract

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 metaanalyses 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 wintermonths 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.

Original languageEnglish (US)
Pages (from-to)17-26
Number of pages10
JournalJournal of Nutrition
Volume143
Issue number1
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

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Vitamin D
Single Nucleotide Polymorphism
Genes
Vitamin D Deficiency
Eye Diseases
Genome-Wide Association Study
Genetic Models
Health
Women's Health
Carotenoids
Practice Guidelines
Observational Studies
Linear Models
Public Health
25-hydroxyvitamin D

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Engelman, C. D., Meyers, K. J., Iyengar, S. K., Liu, Z., Karki, C. K., Igo, R. P., ... Millen, A. E. (2013). Vitamin D intake and season modify the effects of the GC and CYP2R1 genes on 25-hydroxyvitamin D concentrations. Journal of Nutrition, 143(1), 17-26. https://doi.org/10.3945/jn.112.169482

Vitamin D intake and season modify the effects of the GC and CYP2R1 genes on 25-hydroxyvitamin D concentrations. / Engelman, Corinne D.; Meyers, Kristin J.; Iyengar, Sudha K.; Liu, Zhe; Karki, Chitra K.; Igo, Robert P.; Truitt, Barbara; Robinson, Jennifer; Sarto, Gloria E.; Wallace, Robert; Blodi, Barbara A.; Klein, Michael L.; Tinker, Lesley; LeBlanc, Erin S.; Jackson, Rebecca D.; Song, Yiqing; Manson, Joann E.; Mares, Julie A.; Millen, Amy E.

In: Journal of Nutrition, Vol. 143, No. 1, 01.01.2013, p. 17-26.

Research output: Contribution to journalReview article

Engelman, CD, Meyers, KJ, Iyengar, SK, Liu, Z, Karki, CK, Igo, RP, Truitt, B, Robinson, J, Sarto, GE, Wallace, R, Blodi, BA, Klein, ML, Tinker, L, LeBlanc, ES, Jackson, RD, Song, Y, Manson, JE, Mares, JA & Millen, AE 2013, 'Vitamin D intake and season modify the effects of the GC and CYP2R1 genes on 25-hydroxyvitamin D concentrations', Journal of Nutrition, vol. 143, no. 1, pp. 17-26. https://doi.org/10.3945/jn.112.169482
Engelman, Corinne D. ; Meyers, Kristin J. ; Iyengar, Sudha K. ; Liu, Zhe ; Karki, Chitra K. ; Igo, Robert P. ; Truitt, Barbara ; Robinson, Jennifer ; Sarto, Gloria E. ; Wallace, Robert ; Blodi, Barbara A. ; Klein, Michael L. ; Tinker, Lesley ; LeBlanc, Erin S. ; Jackson, Rebecca D. ; Song, Yiqing ; Manson, Joann E. ; Mares, Julie A. ; Millen, Amy E. / Vitamin D intake and season modify the effects of the GC and CYP2R1 genes on 25-hydroxyvitamin D concentrations. In: Journal of Nutrition. 2013 ; Vol. 143, No. 1. pp. 17-26.
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abstract = "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 metaanalyses 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 wintermonths 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.",
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AU - Liu, Zhe

AU - Karki, Chitra K.

AU - Igo, Robert P.

AU - Truitt, Barbara

AU - Robinson, Jennifer

AU - Sarto, Gloria E.

AU - Wallace, Robert

AU - Blodi, Barbara A.

AU - Klein, Michael L.

AU - Tinker, Lesley

AU - LeBlanc, Erin S.

AU - Jackson, Rebecca D.

AU - Song, Yiqing

AU - Manson, Joann E.

AU - Mares, Julie A.

AU - Millen, Amy E.

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