Nutritional rickets: vitamin D, calcium, and the genetic make-up

Pediatr Res. 2017 Feb;81(2):356-363. doi: 10.1038/pr.2016.222. Epub 2016 Nov 3.


Background: The prevalence of vitamin D (vitD) deficiency presenting as rickets is increasing worldwide. Insufficient sun exposure, vitD administration, and/or calcium intake are the main causes. However, vitD system-related genes may also have a role.

Methods: Prospective study: 109 rachitic children completed a 6-mo study period or until rachitic manifestations disappeared. Thirty children were selected as controls. Clinical and biochemical data were evaluated at baseline in patients and controls and biochemistry re-evaluated at radiological healing. Therapy was stratified in three different protocols. Fifty-four single-nucleotide polymorphisms (SNPs) of five vitD system genes (VDR, CP2R1, CYP27B1, CYP24A1, and GC) were genotyped and their association with clinical and biochemcial data was analyzed.

Results: Therapy response was similar in terms of radiological healing although it was not so in terms of biochemical normalization. Only VDR gene (promoter, start-codon, and intronic genotypes) was rickets-associated in terms of serum 25-OH-D, calcium, radiological severity and time needed to heal. Eight patients with sufficient calcium intake and 25-OH-D levels carried a VDR genotype lacking minor allele homozygous genotypes at SNPs spread along the gene.

Conclusion: Although patients presented epidemiologic factors strongly contributing to rickets, genetic modulation affecting predisposition, severity, and clinical course is exerted, at least in part, by VDR gene polymorphic variation.

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics
  • Alleles
  • Calcium / blood*
  • Case-Control Studies
  • Child Nutrition Disorders / genetics*
  • Child Nutrition Sciences
  • Child, Preschool
  • Cholestanetriol 26-Monooxygenase / genetics
  • Cytochrome P450 Family 2 / genetics
  • Female
  • Genotype
  • Homozygote
  • Humans
  • Infant
  • Male
  • Polymorphism, Single Nucleotide
  • Prospective Studies
  • Receptors, Calcitriol / genetics
  • Rickets / diagnosis*
  • Rickets / genetics*
  • Vitamin D / blood*
  • Vitamin D Deficiency / genetics*
  • Vitamin D-Binding Protein / genetics
  • Vitamin D3 24-Hydroxylase / genetics


  • Receptors, Calcitriol
  • Vitamin D-Binding Protein
  • Vitamin D
  • Cytochrome P450 Family 2
  • CYP2R1 protein, human
  • Cholestanetriol 26-Monooxygenase
  • CYP24A1 protein, human
  • Vitamin D3 24-Hydroxylase
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • CYP27B1 protein, human
  • Calcium