title: Nutritional rickets: vitamin D, calcium, and the genetic make-up.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Pediatrics Department, Ain Shams University, Cairo, Egypt.
authors.forename: Mohamed
authors.initials: M
authors.lastname: El Kholy
authors.affiliation: Pediatrics Department, Ain Shams University, Cairo, Egypt.
authors.forename: Heba
authors.initials: H
authors.lastname: Elsedfy
authors.affiliation: Pediatric Endocrinology Research Unit, VHIR (Vall d'Hebron Institut de Recerca), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, CIBERER (Center for Biomedical Research on Rare Diseases), Instituto de Salud Carlos III, Barcelona, Spain.
authors.forename: Monica
authors.initials: M
authors.lastname: Fernández-Cancio
authors.affiliation: Pediatrics Department, Ain Shams University, Cairo, Egypt.
authors.forename: Rasha Tarif
authors.initials: RT
authors.lastname: Hamza
authors.affiliation: Pediatrics Department, Ain Shams University, Cairo, Egypt.
authors.forename: Nermine Hussein
authors.initials: NH
authors.lastname: Amr
authors.affiliation: Pediatrics Department, Ain Shams University, Cairo, Egypt.
authors.forename: Alaa Youssef
authors.initials: AY
authors.lastname: Ahmed
authors.affiliation: Pediatrics Department, Ain Shams University, Cairo, Egypt.
authors.forename: Nadin Nabil
authors.initials: NN
authors.lastname: Toaima
authors.affiliation: Pediatric Endocrinology Research Unit, VHIR (Vall d'Hebron Institut de Recerca), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, CIBERER (Center for Biomedical Research on Rare Diseases), Instituto de Salud Carlos III, Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Audí
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics; D000483:Alleles; D002118:Calcium / Q000097:blood*; D016022:Case-Control Studies; D015362:Child Nutrition Disorders / Q000235:genetics*; D053198:Child Nutrition Sciences; D002675:Child, Preschool; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics; D000072467:Cytochrome P450 Family 2 / Q000235:genetics; D005260:Female; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D018167:Receptors, Calcitriol / Q000235:genetics; D012279:Rickets / Q000175:diagnosis* / Q000235:genetics*; D014807:Vitamin D / Q000097:blood*; D014808:Vitamin D Deficiency / Q000235:genetics*; D014809:Vitamin D-Binding Protein / Q000235:genetics; D065668:Vitamin D3 24-Hydroxylase / Q000235:genetics
chemical_list: D018167:Receptors, Calcitriol; D014809:Vitamin D-Binding Protein; D014807:Vitamin D; D000072467:Cytochrome P450 Family 2; C506833:CYP2R1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; C000600378:CYP27B1 protein, human; D002118:Calcium