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

Authors
  • Wilson, Robin Taylor1
  • Masters, Loren D2
  • Barnholtz-Sloan, Jill S3
  • Salzberg, Anna C4
  • Hartman, Terryl J5
  • 1 Penn State Cancer Institute, Department of Public Health Sciences, Pennsylvania State University College of Medicine, Hershey, Pennsylvania.
  • 2 Penn State Methodology Center, College of Health and Human Development, Pennsylvania State University, University Park, Pennsylvania.
  • 3 Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio.
  • 4 Penn State Institute for Personalized Medicine, Pennsylvania State University College of Medicine, Hershey, Pennsylvania.
  • 5 Rollins School of Public Health, Department of Epidemiology, Emory University, Atlanta, Georgia. , (Georgia)
Type
Published Article
Journal
American journal of epidemiology
Publication Date
Apr 01, 2018
Volume
187
Issue
4
Pages
754–766
Identifiers
DOI: 10.1093/aje/kwx187
PMID: 28673024
Source
Medline
Language
English
License
Unknown

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 D3 (25(OH)D3) and proportion 24,25-dihydroxyvitamin D3 (24,25(OH)2D3)) 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)D3 after adjustment. Only CYP3A43 and VDR polymorphisms were associated with proportion 24,25(OH)2D3. Magnitudes of association with 25(OH)D3 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.

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