Patrice Jones

UV-associated decline in systemic folate: implications for human nutrigenetics, health, and evolutionary processes

The purpose of this study was to examine whether UV exposure alters folate status according to C677T‐MTHFR genotype, and to consider the relevance of this to human health and the evolutionary model of skin pigmentation.

Vitamin D Receptor Genotype Modulates the Correlation between Vitamin D and Circulating Levels of let-7a/b and Vitamin D Intake in an Elderly Cohort

Background and Aims: Circulating microRNAs (miRNAs) are linked to disease and are potential biomarkers. Vitamin D may modulate miRNA profiles, and vitamin D status has been linked to risk of disease, including cardiovascular disease and cancers. We hypothesise that genotypic variance influences these relationships. We examined the correlations between vitamin D intake and circulating levels of the miRNAs let-7a/b, and the involvement of two common vitamin D receptor (VDR) polymorphisms, BsmI and ApaI. Methods: Two hundred participants completed food frequency and supplement questionnaires, and were assayed for circulating let-7b expression by qPCR. Polymorphisms were detected using restriction fragment length polymorphism-PCR. Results: let-7b expression negatively correlated with vitamin D intake (rs = -0.20, p = 0.005). The magnitude and direction of correlation were maintained in the presence of the BsmI restriction site (rs = -0.27, p = 0.0005). However, in the absence of BsmI restriction site, the direction of the correlation was reversed (rs = +0.319, p = 0.0497). These correlations were significantly different (z-score = 2.64, p = 0.0085). The correlation between vitamin D intake and let-7a was only significant in those without the ApaI restriction site. Conclusions: The correlation between vitamin D intake and let-7a/b expression in this cohort varies with VDR genotype. This study highlights the importance of considering underlying genotypic variance in miRNA expression studies and in nutritional epigenetics generally.

Vitamin D Beyond Metabolism

Interest in vitamin D and the VDR gene is increasing as putative roles in human health and evolutionary processes are explored. This review looks beyond the classic biochemistry that links vitamin D to calcium homeostasis; it explores how vitamin D interacts with light in a broader perspective than simple skin photosynthesis. It examines how the vitamin influences circadian rhythm, and how it may have helped drive the evolution of skin pigmentation. To this end, the nutrient–nutrient relationship with folate is also explored. The VDR gene is additionally examined as a factor in the evolutionary selection of skin depigmentation at higher latitudes to allow vitamin D synthesis. Evidence is given to show that VDR polymorphisms exhibit a latitudinal gradient in allele prevalence consistent with such a paradigm. Overall, the review examines new evo-devo ideas that link light-sensitive vitamins to human health/phenotype, both within and across the lifecycle.

Frequency of folate-related polymorphisms varies by skin pigmentation

Folate‐mediated 1‐carbon transfer processes are vital in human health but are susceptible to independent and interactive influences of genetic variance and environmental exposures. Evidence suggests folate levels may be impacted by genetic variance and environmental UVR, with the effect of UVR levels influenced in part by degree of skin pigmentation. Folate‐related genes are also influenced by UVR levels; however, the potential relationship between key folate‐related genes and skin pigmentation has not yet been explored. The purpose of this study was to examine potential associations between frequencies of key folate variants and degree of skin pigmentation.

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

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.

B vitamins and pollution, an interesting, emerging, yet incomplete picture of folate and the exposome

We read the interesting article by Zhong et al. (1) describing how B-vitamin supplementation reduces the adverse epigenetic response to fine particles associated with air pollution. However, we feel it is extremely premature to suggest, as the authors do, that “individual-level prevention” via vitamin supplements “might be used as prevention to complement [environmental] regulations to attenuate the impact of air pollution” (1).

Photobiology of vitamins

This review explores contemporary ideas about the relationship between light exposure and vitamin biology. Nutritional biochemistry has long recognized the relationship between vitamins A and D and light exposure, but in recent years other vitamins have also been implicated in photoresponsive biological mechanisms that influence health, well-being, and even evolutionary processes. Interactions between light and vitamins can modify genotype-phenotype relationships across the life cycle, providing a basis for interesting new explanations relevant to wide aspects of human biology. This review examines both well-established and emerging ideas about vitamin photobiology in the context of the following: (1) light responsiveness of vitamin D (photosynthesized in skin), vitamin A (linked to vision), and vitamin B3 (needed to repair genomic damage); (2) vulnerability of folate and vitamins B1, B2, B12, and D to ultraviolet (UV) light (all potentially degraded); (3) protective/filtering actions of carotenoids and vitamins C and E, which act as antioxidants and/or natural sunscreens, against UV light; (4) role of folate, carotenoids, and vitamins A, B3, C, D, and E in UV-related genomic regulation, maintenance, and repair; (5) role of folate and vitamins A, B2, B12, and D in a range of light-signaling and light-transduction pathways; and (6) links between folate and vitamin D and the evolution of UV light-adaptive phenotypes.

The Vitamin D–Folate Hypothesis as an Evolutionary Model for Skin Pigmentation: An Update and Integration of Current Ideas

Vitamin D is unique in being generated in our skin following ultraviolet radiation (UVR) exposure. Ongoing research into vitamin D must therefore always consider the influence of UVR on vitamin D processes. The close relationship between vitamin D and UVR forms the basis of the “vitamin D–folate hypothesis”, a popular theory for why human skin colour has evolved as an apparent adaption to UVR environments. Vitamin D and folate have disparate sensitivities to UVR; whilst vitamin D may be synthesised following UVR exposure, folate may be degraded. The vitamin D–folate hypothesis proposes that skin pigmentation has evolved as a balancing mechanism, maintaining levels of these vitamins. There are several alternative theories that counter the vitamin D–folate hypothesis. However, there is significant overlap between these theories and the now known actions of vitamin D and folate in the skin. The focus of this review is to present an update on the vitamin D–folate hypothesis by integrating these current theories and discussing new evidence that supports associations between vitamin D and folate genetics, UVR, and skin pigmentation. In light of recent human migrations and seasonality in disease, the need for ongoing research into potential UVR-responsive processes within the body is also discussed.

Vitamin D and folate: A reciprocal environmental association based on seasonality and genetic disposition

The purpose of this study was (1) to elucidate any reciprocal seasonal relationship that might exist between red cell folate (RCF) and serum vitamin D3 Levels; (2) to explore whether folate‐related gene variants that influence/alter DNA‐thymidylate and methyl group biosynthesis modify any associations detected in objective 1; and (3) to consider whether these processes might influence reproductive success consistent with the “folate‐vitamin D‐UV hypothesis of skin pigmentation” evolutionary model.

Acknowledgement to the Reviewers

Chris T. Bolliger, Tygerberg, South Africa Raphael Borie, Paris, France Piera Boschetto, Ferrara, Italy Gabriel T. Bosslet, Indianapolis, USA Louis-Philippe Boulet, Sainte-Foy, Canada A. Bourdin, Montpellier, France John Brannan, Sydney, Australia Joerg Brederlau, Berlin, Germany E.C. Breen, La Jolla, USA Fabienne Bregeon, Marseille, France Pilar Brito-Zeron, Barcelona, Spain Dunja Bruder, Braunschweig, Germany Guy G. Brusselle, Gent, Belgium Martin H. Brutsche, St. Gallen, Switzerland Antonio Bugalho, Lisbon, Portugal Janette Burgess, Camperdown, Australia Umberto Campia, Chicago, USA Giorgio Walter Canonica, Genova, Italy Andre Capderou, Le Plessis Robinson, France Gaetano Caramori, Ferrara, Italy Pierluigi Carratu, Bari, Italy Laura Carrozzi, Pisa, Italy C.R.F. Carvalho, Sao Paulo, Brazil Gian Luca Casoni, Forli, Italy Loris Ceron, Carbonera, Italy Stefania Cerri, Portland, USA Indranil Chakravorty, London, UK Rachel Chambers, London, UK Shi-Chuan Chang, Taipei, Taiwan Ling Chen, Baltimore, USA Alfredo Chetta, Parma, Italy Carlo Chezzi, Parma, Italy Prashant N. Chhajed, Mumbai, India Doo-Sup Choi, Rochester, USA Marco Matteo Ciccone, Bari, Italy Michal Ciurzynski, Warsaw, Poland Donald W. Cockcroft, Saskatoon, Canada Henri Colt, Irvine, USA Alison Condliffe, Cambridge, UK Marco Confalonieri, Trieste, Italy Claudius Conrad, Boston, USA Vittoria Conti, Rome, Italy Robalo Cordeiro, Coimbra, Portugal Massimo Corradi, Parma, Italy Raja Abboud, Vancouver, Canada Yossef Aelony, Rancho Palos Verdes, USA Michalis Agrafiotis, Magoula, Greece Khalid Al Shafi, London, UK Ghada Alsaleh, Illkirch, France Nicolino Ambrosino, Cisanello, Pisa, Italy Kayvan Amjadi, Ottawa, Canada Asha Anandiah, Boston, USA Stephan Andreas, Immenhausen, Germany Jouke T. Annema, Leiden, The Netherlands Katerina Antoniou, Heraklion, Greece Balazs Antus, Budapest, Hungary Juan Carlos Arevalo, Salamanca, Spain Christine Armbruster, Vienna, Austria Laurent Arnaud, Paris, France Hormoz Ashtyani, Hackensack, USA John D. Aubert, Lausanne, Switzerland Najib Ayas, Vancouver, Canada Imran Aziz, Wigan, UK Chung-Xue Bai, Shanghai, China Kristina Bailey, Omaha, USA Petros Bakakos, Athens, Greece Bruno Balbi, Veruno, Italy Ferran Barbe, Lleida, Spain Xavier Basagana Flores, Barcelona, Spain Sandip Basu, Bombay, India Salvatore Battaglia, Palermo, Italy Sevim Bavbek, Ankara, Turkey Gillian Beamer, Columbus, USA H.D. Becker, Heidelberg, Germany Jurgen Behr, Bochum, Germany Carolyn Behrendt, Duarte, USA Maria Belvisi, London, UK Norbert Berend, Glebe, Australia Gidon Berger, Haifa, Israel Robert Berkowitz, Hackensack, USA Nitin Bhatt, Columbus, USA Luca Bianchi, Lumezzane, Italy Andrea Bianco, Campobasso, Italy Semra Bilaceroglu, Izmir, Turkey Jose Blanquer, Valencia, Spain Alexander Blau, Berlin, Germany Konrad E. Bloch, Zurich, Switzerland