Background: Little is known regarding factors associated with calcitriol and a relative measure of calcitriol, the calcitriol-24,25-dihydroxyvitamin D3-calcifediol proportion ratio (C24CPR). Methods: Using a cross-sectional study design, healthy young adults of African and European descent, matched (1:1) on age (+/- 5 years) provided a blood sample in non-summer months (N=376). Vitamin D metabolites were measured in plasma with high performance liquid chromatography/tandem mass spectrometry (HPLC/MS-MS). West African genetic ancestry proportion (WGA) was estimated using STRUCTURE modeling of genetic ancestry-informative markers. Multivariable regression models were used to estimate the association of WGA and vitamin D-pathway gene variants with calcitriol and C24CPR, controlling for days from summer solstice, age, sex, blood pressure, body mass index, dietary vitamin D intake, oral contraceptive/medroxyprogesterone acetate use, smoking, tanning bed use, and time of day. Results: Calcitriol and C24CPR were not highly correlated (rho=0.14), although both were significantly, positively, and monotonically associated with WGA (p-trends 0.025 and <0.001, respectively). In fully adjusted models, genetic factors explained a greater proportion of variability in C24CPR (R2=0.121 and 0.310, respectively). Variants in genes with associated with calcitriol (CALB1, CYP27B1, GC, PPARGC1A) differed from those associated with C24CPR (CYP3A43, FGF23, KL, VDR). Conclusions: Both absolute and relative measures of calcitriol were significantly higher among African Americans. Otherwise, these biomarkers appear to be genetically distinct. Impact: C24CPR may be better suited to personalized medicine, due to a higher proportion of population variability explained by genetic variation and a less skewed distribution.
