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.

Abstract

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.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cross-Sectional Studies
  • DNA Methylation / radiation effects*
  • Female
  • Humans
  • Male
  • New South Wales
  • Polymorphism, Genetic*
  • Receptors, Calcitriol / genetics*
  • Ultraviolet Rays / adverse effects*

Substances

  • Receptors, Calcitriol
  • VDR protein, human