Associations of vitamin D receptor gene polymorphism with idiopathic hypercalciuria in children

Abstract

Introduction. Idiopathic hypercalciuria (IH) is one of the most common metabolic disorders in children and can lead to the development of urolithiasis over childhood. In this regard, studying the etiology of this pathological condition will help to prevent the development of IH and reduce the risk of developing urolithiasis.
 Study purpose: to study the role of genetic polymorphisms of the VDR gene in the development of IH in children and their relatives of the first and second lines of kinship.
 Materials and methods. The study included 68 people, including 35 children aged of 3 to 17 years with identified hypercalciurine and 33 first- and second-line relatives with IH and urolithiasis. A study of the level of 25-OH vitamin D in blood plasma and a genetic study for the presence of polymorphisms of the vitamin D receptor gene VDR were carried out including: BsmI Polymorphism IVS10+283G>A, A-3731G (Cdx2), FokI Polymorphism; Ex4+4T>C. To compare the frequency of occurrence of vitamin D receptor (VDR) genotypes, samples of conditionally healthy individuals permanently residing in Kemerovo and natives of the European part of the Russian Federation were taken. At the same time, for the VDR G283A (BsmI) gene, a healthy sample consisted of 232 people from Kemerovo and 96 cases from the European part of Russia, for the VDR A-3731G gene — 269 and 243 people, and for the VDR FokI TC gene — 172 and 96 people, respectively. 
 Results. Reducing the content of 25(OH)D in the blood of less than 30 ng/ml was detected in 33 (48.5%) IH children. 25 (OH)D level below 20 ng/ml was detected in 15 (22.1%) patients. In IH patients and level 25(OH)D in the blood of less than 20 ng/ml, the homozygous variant 283 GG of the VDR gene (BsmI) was found in 20% of the examined versus 51% (p = 0.028) of conditionally healthy individuals. The heterozygous genotype of 283 PA of the VDR gene (BsmI) was determined in 73.3% of IH patients versus 41.7% of conditionally healthy individuals (p = 0.027). The heterozygous Ex4+4TC genotype of the VDR Fokl gene was recorded in 66.7% of the examined IH patients and low serum vitamin D levels (< 20 ng/ml) when compared with the level in conditionally healthy individuals (p = 0.030). In patients with low vitamin D levels against IH background, the proportion of the minor allele A 283 of the VDR gene (BsmI) was determined significantly more often than in healthy individuals (p = 0.044).
 Conclusion. A relationship was identified between polymorphism of the vitamin D receptor gene VDR (polymorphic marker BsmI (rs1544410) of the VDR gene 283G>A; polymorphic marker Fokl (rs2228570) of the VDR gene Ex4+4T>C) with IH and deficiency of 25(OH)D levels in the blood serum of children.