Оцінка ризику розвитку соматотропної недостатності залежно від розподілу частот алелей і генотипів поліморфного локусу rs1544410 BsmI гена рецептора вітаміну D

Abstract

Growth hormone deficiency (GHD) is a disease caused by a significant disturbance in the growth hormone (GH) /growth factor system, it occures as a result of various hereditary or acquired causes and is characterized, first of all, by a significant delay in the child's growth and physical development. GHD can be isolated or combined with deficiency of other adenohypophysis hormones. The presence of a relationship between the GH /growth factor system and vitamin D (vit D) determines the involvement of genetic changes in the vit D receptor (VDR) in the pathogenesis of GHD. Purpose - to assess the risk of developing GHD based on the investigation of the distribution of allele frequencies and genotypes of the polymorphic locus rs1544410 BsmI of the VDR gene. Materials and methods. The determination of VDR BsmI gene (rs1544410) polymorphism was performed using the polymerase chain reaction method, followed by analysis of the length of restriction fragments upon their detection by agarose gel electrophoresis in 22 prepubertal children with GHD. The serum 25-hydroxycalciferol (25(OH)D) level was determined by immunochemiluminescent method on microparticles (Abbott, USA). Results. G/A allele was most often found in children with isolated GHD and multiple pituitary insufficiency (MPH) (43.8% and 83.3%, respectively). In the presence of G/A and G/G genotypes, the risk of GHD is reliably high: OR=3.60 (95% CI 1.40-9.23); OR=10.69 (95% CI 2.34-48.85) respectively; with the A/A genotype variant the risk of GHD is reliably low OR=0.11 (95% CI 0.04-0.33). Carrying the G allele of the polymorphic locus rs1544410 Bsm I of the VDR gene is associated with the risk of developing GHD OR=5.58 (95% CI 4.51-6.90; p<0.001). A significantly difference in the peak GH release was established in patients carrying the G/G and A/A, G/G and G/A alleles. 83.33% of children with MPH and 68.49% with isolated GHD had hypovitaminosis D. Vit D deficiency was recorded in carriers of all three types of alleles. Conclusions. In the presence of G/A and G/G genotypes, the risk of GHD increases, in the presence of the A/A genotype, it decreases. The G allele carrier of the polymorphic locus rs1544410 Bsm I of the VDR gene is associated with the risk of developing GHD OR=5.58 (95% CI 4.51-6.90; p<0.001), despite the ideal distribution of genotypes. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of all participating institutions. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.