Ancestry-Adjusted Vitamin D Metabolite Concentrations in Association with Cytochrome P450 3A Polymorphisms

Robin Taylor Wilson, Loren D. Masters, Jill S. Barnholtz-Sloan, Anna C. Salzberg, Terryl Johnson Hartman

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

We investigated the association between genetic polymorphisms in cytochrome P450 (CYP2R1, CYP24A1, and the CYP3A family) with nonsummer plasma concentrations of vitamin D metabolites (25-hydroxyvitamin D 3 (25(OH)D 3) and proportion 24,25-dihydroxyvitamin D 3 (24,25(OH) 2 D 3)) among healthy individuals of sub-Saharan African and European ancestry, matched on age (within 5 years; n = 188 in each ancestral group), in central suburban Pennsylvania (2006-2009). Vitamin D metabolites were measured using high-performance liquid chromatography with tandem mass spectrometry. Paired multiple regression and adjusted least-squares mean analyses were used to test for associations between genotype and log-transformed metabolite concentrations, adjusted for age, sex, proportion of West-African genetic ancestry, body mass index, oral contraceptive (OC) use, tanning bed use, vitamin D intake, days from summer solstice, time of day of blood draw, and isoforms of the vitamin D receptor (VDR) and vitamin D binding protein. Polymorphisms in CYP2R1, CYP3A43, vitamin D binding protein, and genetic ancestry proportion remained associated with plasma 25(OH)D 3 after adjustment. Only CYP3A43 and VDR polymorphisms were associated with proportion 24,25(OH) 2 D 3. Magnitudes of association with 25(OH)D 3 were similar for CYP3A43, tanning bed use, and OC use. Significant least-squares mean interactions (CYP2R1/OC use (P = 0.030) and CYP3A43/VDR (P = 0.013)) were identified. A CYP3A43 genotype, previously implicated in cancer, is strongly associated with biomarkers of vitamin D metabolism. Interactive associations should be further investigated.

Original languageEnglish (US)
Pages (from-to)754-766
Number of pages13
JournalAmerican journal of epidemiology
Volume187
Issue number4
DOIs
StatePublished - Apr 1 2018

All Science Journal Classification (ASJC) codes

  • Epidemiology

Fingerprint Dive into the research topics of 'Ancestry-Adjusted Vitamin D Metabolite Concentrations in Association with Cytochrome P450 3A Polymorphisms'. Together they form a unique fingerprint.

  • Cite this

    Wilson, R. T., Masters, L. D., Barnholtz-Sloan, J. S., Salzberg, A. C., & Hartman, T. J. (2018). Ancestry-Adjusted Vitamin D Metabolite Concentrations in Association with Cytochrome P450 3A Polymorphisms. American journal of epidemiology, 187(4), 754-766. https://doi.org/10.1093/aje/kwx187