TY - JOUR
T1 - Genetic Factors Associated with Absolute and Relative Plasma Concentrations of Calcitriol
AU - Wilson, Robin Taylor
AU - Safford, Susan E.
AU - Ostrom, Quinn T.
AU - Wang, Ming
AU - McDonald, Alicia C.
AU - Salzberg, Anna C.
AU - Barnholtz-Sloan, Jill S.
AU - Richie, John P.
N1 - Publisher Copyright:
©2023 American Association for Cancer Research.
PY - 2023/5/1
Y1 - 2023/5/1
N2 - 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 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 (Ptrend 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, and PPARGC1A) differed from those associated with C24CPR (CYP3A43, FGF23, KL, and 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.
AB - 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 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 (Ptrend 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, and PPARGC1A) differed from those associated with C24CPR (CYP3A43, FGF23, KL, and 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.
KW - Calcifediol/metabolism
KW - Calcitriol/metabolism
KW - Cross-Sectional Studies
KW - Humans
KW - Receptors, Calcitriol/genetics
KW - Vitamin D
KW - Vitamins
KW - Young Adult
UR - https://www.scopus.com/pages/publications/85159251015
UR - https://pubmed.ncbi.nlm.nih.gov/36788426/
U2 - 10.1158/1055-9965.EPI-22-0797
DO - 10.1158/1055-9965.EPI-22-0797
M3 - Article
C2 - 36788426
SN - 1055-9965
VL - 32
SP - 697
EP - 707
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 5
ER -