Distribution of variants in multiple vitamin D-related loci (DHCR7/NADSYN1, GC, CYP2R1, CYP11A1, CYP24A1, VDR, RXRα and RXRγ) vary between European, East-Asian and Sub-Saharan African-ancestry populations

Jones, Patrice; Lucock, Mark; Chaplin, George; Jablonski, Nina G.; Veysey, Martin; Scarlett, Christopher; Beckett, Emma

Abstract

Background
The frequency of vitamin D-associated gene variants appear to reflect changes in long-term ultraviolet B radiation (UVB) environment, indicating interactions exist between the primary determinant of vitamin D status, UVB exposure and genetic disposition. Such interactions could have health implications, where UVB could modulate the impact of vitamin D genetic variants identified as disease risk factors. However, the current understanding of how vitamin D variants differ between populations from disparate UVB environments is limited, with previous work examining a small pool of variants and restricted populations only.

Methods
Genotypic data for 46 variants within multiple vitamin D-related loci (DHCR7/NADSYN1, GC, CYP2R1, CYP11A1, CYP27A1, CYP24A1, VDR, RXRα and RXRγ) was collated from 60 sample sets (2633 subjects) with European, East Asian and Sub-Saharan African origin via the NCBI 1000 Genomes Browser and ALFRED (Allele Frequency Database), with the aim to examine for patterns in the distribution of vitamin D-associated variants across these geographic areas.

Results
The frequency of all examined genetic variants differed between populations of European, East Asian and Sub-Saharan African ancestry. Changes in the distribution of variants in CYP2R1, CYP11A1, CYP24A1, RXRα and RXRγ genes between these populations are novel findings which have not been previously reported. The distribution of several variants reflected changes in the UVB environment of the population’s ancestry. However, multiple variants displayed population-specific patterns in frequency that appears not to relate to UVB changes.

Conclusions
The reported population differences in vitamin D-related variants provides insight into the extent by which activity of the vitamin D system can differ between cohorts due to genetic variance, with potential consequences for future dietary recommendations and disease outcomes.

Citation

Jones, P., Lucock, M., Chaplin, G., Jablonski, N. G., Veysey, M., Scarlett, C., & Beckett, E. (2020). Distribution of variants in multiple vitamin D-related loci (DHCR7/NADSYN1, GC, CYP2R1, CYP11A1, CYP24A1, VDR, RXRα and RXRγ) vary between European, East-Asian and Sub-Saharan African-ancestry populations. Genes and Nutrition, 15(1), Article 5. https://doi.org/10.1186/s12263-020-00663-3

• Journal Article Type: Article
• Acceptance Date: Feb 28, 2020
• Online Publication Date: Mar 13, 2020
• Publication Date: Mar 13, 2020
• Deposit Date: May 6, 2020
• Publicly Available Date: May 7, 2020
• Journal: Genes & Nutrition
• Print ISSN: 1555-8932
• Publisher: BioMed Central
• Peer Reviewed: Peer Reviewed
• Volume: 15
• Issue: 1
• Article Number: 5
• DOI: https://doi.org/10.1186/s12263-020-00663-3
• Keywords: Vitamin D; Polymorphism; UVB; Skin pigmentation
• Public URL: https://hull-repository.worktribe.com/output/3503693
• Publisher URL: https://genesandnutrition.biomedcentral.com/articles/10.1186/s12263-020-00663-3
• Additional Information: Received: 17 September 2019; Accepted: 28 February 2020; First Online: 13 March 2020; : Not applicable.; : Not applicable.; : The authors declare that they have no competing interests.