Involvement of the vitamin D receptor gene in the development of idiopathic short stature

Abstract

Background. The vitamin D receptor (VDR) gene is localized in the chromosome 12 (region 12q13). Its polymorphic variants BsmI and FokI are the most promising in clinical and diagnostic terms. During normal ontogenesis, the VDR gene affects the total bone content in the body and its resulting length determined by the development of the skeleton. The aim of the study was to assess genotypic features in children with idiopathic short stature. Materials and methods. Determination of the BsmI polymorphism in the VDR gene (rs1544410) was performed by polymerase chain reaction followed by analysis of the length of restriction fragments when detected by agarose gel electrophoresis in 18 prepubertal children with idiopathic short stature. Results. In the group of children with idiopathic short stature, the proportion of the GG genotype is four times higher than in the control group. In children of the G/A heterozygotes, the risk of idiopathic short stature is significantly high (odds ratio (OR)=6.00; 95% confidence interval (CI) 2.06–17.48; p<0.01); in the G/G variant, it is high but not significant (OR=4.54; 95% CI 0.70–29.31; p=0.11). Patients with the AA genotype were three times less than in the control group, indicating that the AA homozygotes have a threefold reduction in the risk of idiopathic short stature compared to an empirical risk. The frequency of the G allele in patients (qG=0.444) is almost three times higher than in the group of healthy individuals (qG=0.152), indicating that the carriage of the G allele of the rs1544410 BsmI polymorphic locus of the VDR gene is significantly associated with the risk of developing idiopathic short stature (OR=4.46; 95% CI 3.60–5.51; p<0.001). Conclusions. In children with the G/A and G/G genotypes, the risk of idiopathic short stature increases, and the presence of the A/A genotype is a protective polymorphism against idiopathic short stature. Carriage of the G allele of the rs1544410 BsmI polymorphic locus of the VDR gene is associated with the risk of idiopathic short stature, despite the almost perfect distribution of genotypes.