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Research Abstracts Online
January 2008 - March 2009

University of Minnesota Twin Cities
School of Public Health
Division of Epidemiology and Community Health

PI: Kimberly Robien

Evaluating Vitamin D Exposure and Metabolism: A Pilot Study

Vitamin D, a sterol hormone precursor, is known to have anti-proliferative and pro-differentiation activities at the cellular level; thus, there may be a relationship between vitamin D and the risk of cancers. Current knowledge suggests that the nutrient could play a significant role in public health recommendations for cancer prevention, as well as bone health. The primary naturally occurring source of vitamin D is sunlight, yet most epidemiologic studies of vitamin D and cancer have relied on self-reported dietary measures alone. The lack of information on sun exposure and genetic variation in the vitamin D biosynthesis pathway are major limitations of the current scientific evidence.

The specific aims of this pilot project were to compare questionnaire data collected on all-source vitamin D exposures (UV radiation, diet, and supplements) to serum 25-hydroxycholecalciferol levels in order to assess the accuracy of the questionnaire; and to determine whether genetic variants in the vitamin D biosynthesis pathway (CYP2R1, CYP27A1, CYP27B1, and vitamin D binding protein) are associated with alterations in serum 25-hydroxycholecalciferol (25OHD) and 1,25-dihydroxycholecalciferol levels.    

In a multivariate analysis, age, BMI, month of blood draw, usual dietary vitamin D intake, supplemental vitamin D intake, and self-reported daily sun exposure in the month prior to blood draw explained 53% of the variance (R2) in serum 25OHD levels.

16% of the variance in serum 1,25(OH)2D levels were explained with a model that included age, sex, and BMI. The 25OHD metabolite is the primary circulating form of vitamin D, whereas the metabolically active 1,25(OH)2D form is present only in picomolar quantities, and is tightly regulated in order to maintain calcium homeostasis.  Thus, it is not surprising that the ability to predict serum 1,25(OH)2D levels is considerably lower than that of 25OHD.

Of the 55 primary SNPs evaluated in this study, only six SNPs were found to be significantly associated with 25OHD concentrations: CYP2R1 rs10741657 and rs1993116, and VDR rs2853564, rs4760658, rs7299460, and rs11168287.

As multiple SNPs were explored in this relatively small pilot study, some of the findings may be spurious and caution should be employed in interpreting the results. However, the results indicate that genetic variation in the entire vitamin D pathway (not simply the VDR gene) contribute to circulating vitamin D levels, and should be explored in greater detail.