Genetic Influences on Circulating Vitamin D Level: A Review
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GENETICS (C NEWTON-CHEH AND G SMITH, SECTION EDITORS)
Genetic Influences on Circulating Vitamin D Level: A Review Feng Zhang & Alireza Moayyeri & Timothy D. Spector
Published online: 11 October 2012 # Springer Science+Business Media New York 2012
Abstract Over the last decade, there has been renewed interest in vitamin D due to increasing evidence of its importance in a wide range of health outcomes in addition to its traditional role in bone health. Although environmental factors play important roles in determining vitamin D levels, recent large-scale genetic studies also confirmed strong genetic influences. Recent genome-wide association studies (GWAS) have found genetic variations associated with vitamin D metabolism on several genes such as 7 dehydrochlesterol reductase (DHCR7), vitamin D binding protein (GC), 25-hydroxlase (CYP2R1), and 24hydroxylase (CYP24A1). Vitamin D receptor (VDR), 25hydroxyvitamin D 1-α hydroxylase (CYP27B1) and another 25- and 24-hydroxylase (CYP3A4) have also shown significant association in various candidate gene studies. Despite recent success in genetic studies, currently identified genes could only explain a small fraction of genetic variation in 25-hydroxyvitamin D level. With advances in next generation sequencing technologies, additional genetic variants and epigenetic mechanisms are expected to further reveal the genetic architecture of vitamin D metabolism.
F. Zhang (*) : A. Moayyeri : T. D. Spector Department of Twin Research & Genetic Epidemiology, King’s College London, St Thomas’ Hospital Campus, 1st Floor South Wing Block 4, Westminster Bridge Road, London SE1 7EH, UK e-mail: [email protected] A. Moayyeri e-mail: [email protected] T. D. Spector e-mail: [email protected] F. Zhang Division of Genetics and Epidemiology, Institute of Cancer Research, Belmont, Sutton, Surrey SM2 5NG, UK
Keywords Genetics . Vitamin D . 25-hdyroxyvitamin D . Metabolism . Single nucleotide polymorphisms . Genome-wide association study
Introduction In the past decade, there has been renewed interest in the “sunshine” vitamin, vitamin D, as the proliferation of published studies suggested its pleiotropic effects on a wide range of phenotypes in addition to its important role in musculoskeletal health. Vitamin D insufficiency is prevalent worldwide and affects almost 50 % of the population across all ethnicities and age groups [1]. High prevalence of vitamin D insufficiency is an increasingly important public health issue because hypovitaminosis D is an independent risk factor for total mortality in the general population [2] as well as a wide of range of disease such as hypertension, dyslipidaemia, cancers, fractures and falls, autoimmune diseases, type-2 diabetes, and depression [3–13]. These epidemiologic associations have been supported by observations of molecular mechanisms of vitamin D action across different target organs [3–13]. As a complex trait, both environmental and genetic components contribute to vitamin D level variation. The majority of vitamin D (approximately
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