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

• Published in: Pediatric research Vol. 81; no. 2; pp. 356 - 363
• Main Authors: El Kholy, Mohamed, Elsedfy, Heba, Fernández-Cancio, Monica, Hamza, Rasha Tarif, Amr, Nermine Hussein, Ahmed, Alaa Youssef, Toaima, Nadin Nabil, Audí, Laura
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.02.2017; Nature Publishing Group
• Subjects: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase - genetics; 631/208/727/2000; 631/443/810; 692/699/1670/316; 692/699/1702; Alleles; Calcium; Calcium - blood; Case-Control Studies; Child Nutrition Disorders - genetics; Child Nutrition Sciences; Child, Preschool; Cholestanetriol 26-Monooxygenase - genetics; Cytochrome P450 Family 2 - genetics; Female; Genetics; Genotype; Homozygote; Humans; Infant; Male; Medical research; Medicine & Public Health; Pediatric Surgery; Pediatrics; Polymorphism, Single Nucleotide; Prospective Studies; Receptors, Calcitriol - genetics; Rickets - diagnosis; Rickets - genetics; translational-investigation; Vitamin D; Vitamin D - blood; Vitamin D Deficiency - genetics; Vitamin D-Binding Protein - genetics; Vitamin D3 24-Hydroxylase - genetics; Vitamin deficiency
• ISSN: 0031-3998; 1530-0447
• DOI: 10.1038/pr.2016.222

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.