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.
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.
Authors: F Sentinelli; L Bertoccini; I Barchetta; D Capoccia; M Incani; M G Pani; S Loche; F Angelico; M Arca; S Morini; E Manconi; A Lenzi; E Cossu; F Leonetti; M G Baroni; M G Cavallo Journal: Nutr Metab Cardiovasc Dis Date: 2016-02-19 Impact factor: 4.222
Authors: André G Uitterlinden; Yue Fang; Joyce B J van Meurs; Hans van Leeuwen; Huibert A P Pols Journal: J Steroid Biochem Mol Biol Date: 2004-05 Impact factor: 4.292