UV at time of conception associated with Vitamin D Receptor activation 65 years later – Sept 2017

VDR gene methylation as a molecular adaption to light exposure: Historic, recent and genetic influences.

Am J Hum Biol. 2017 Sep 10;29(5). doi: 10.1002/ajhb.23010. Epub 2017 Apr 22.

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OBJECTIVES:
The vitamin D receptor (VDR) is a member of the nuclear receptor family of transcription factors. We examined whether degree of VDR gene methylation acts as a molecular adaptation to light exposure. We explored this in the context of photoperiod at conception, recent UV irradiance at 305 nm, and gene-latitude effects.

METHODS:
Eighty subjects were examined for VDR gene-CpG island methylation density. VDR gene variants were also examined by PCR-RFLP.

RESULTS:
Photoperiod at conception was significantly positively related to VDR methylation density, explaining 17% of the variance in methylation (r2  = 0.17; P = .001). Within this model, photoperiod at conception and plasma 25(OH)D independently predicted methylation density at the VDR-CpG island. Recent UV exposure at 305 nm led to a fivefold increase in mean methylation density (P = .02). Again, UV exposure and plasma 25(OH)D independently predicted methylation density at the VDR-CpG island. In the presence of the BsmI mutant allele, methylation density was increased (P = .01), and in the presence of the TaqI or FokI mutant allele, methylation density was decreased (P = .007 and .04 respectively). Multivariate modelling suggests plasma 25(OH)D, photoperiod at conception, recent solar irradiance, and VDR genotype combine as independent predictors of methylation at the VDR-CpG island, explaining 34% of the variance in methylation (R2  = 0.34, P < .0001).

CONCLUSIONS:
Duration of early-life light exposure and strength of recent irradiance, along with latitudinal genetic factors, influence degree of VDR gene methylation consistent with this epigenetic phenomenon being a molecular adaptation to variation in ambient light exposure. Findings contribute to our understanding of human biology.

Beckett EL1,2,3, Jones P1, Veysey M2,4, Duesing K3, Martin C1, Furst J5, Yates Z6, Jablonski NG7, Chaplin G7, Lucock M1.
1 School of Environmental & Life Sciences, University of Newcastle, PO Box 127, Brush Rd, Ourimbah, NSW, 2258, Australia.
2 Medicine and Public Health, University of Newcastle, PO Box 127, Brush Rd, Ourimbah, NSW, 2258, Australia.
3 Food and Nutrition Flagship, CSIRO, NSW, Australia.
4 Teaching & Research Unit, Central Coast Local Health District, PO Box 361, Gosford, NSW, 2250, Australia.
5 Maths & Physical Sciences, University of Newcastle, PO Box 127, Brush Rd, Ourimbah, NSW, 2258, Australia.
6 Biomedical Sciences & Pharmacy, University of Newcastle, PO Box 127, Brush Rd, Ourimbah, NSW, 2258, Australia.
7 Anthropology Department, The Pennsylvania State University, 409 Carpenter Building, University Park, Pennsylvania, 16802.