EP1211 - ECE_3181 - Clinical and genetic aspects of growth hormone deficiency in children: the role of VDR polymorphisms

Abstract

In recent years, vitamin D (vit. D) and the vitamin D receptor gene (VDR) have attracted considerable scientific interest due to their involvement not only in calcium–phosphorus homeostasis but also in growth regulation. Vitamin D is known to influence the differentiation of somatotroph cells in the pituitary gland, hepatic production of insulin-like growth factor 1 (IGF-1), and physiological processes of cartilage remodeling. The VDR gene contains several polymorphic variants, among which BsmI (rs1544410), TaqI (rs731236), and ApaI (rs7975232), located in the 3′ untranslated region, are the most extensively studied. These polymorphisms may modulate VDR expression and mRNA stability, thereby affecting the biological activity of vitamin D. The aim of this study was to assess the effect of combined VDR gene polymorphisms (BsmI, TaqI, and ApaI) on hormonal, metabolic, and biochemical parameters in children with growth hormone deficiency (GHD). The study included 42 children with confirmed GHD. Genotyping of VDR polymorphisms was performed using PCR followed by restriction fragment length polymorphism analysis and agarose gel electrophoresis. The most frequent combined genotype was the heterozygous variant (G/A + T/C + A/C), observed in 55.56% of patients, whereas the homozygous pathological genotype (A/A + C/C + A/A) was the least common (16.66%). Children carrying the pathological homozygous genotype demonstrated the lowest basal and stimulated growth hormone levels, indicating a more pronounced hormonal deficiency. Decreased serum 25(OH)D concentrations were identified in all genotype groups. Vitamin D deficiency predominated in children with the normal genotype, while insufficiency was more frequently observed in carriers of heterozygous and homozygous variants. Correlation analysis revealed significant associations between vit. D levels and IGF-1, growth hormone, body mass index, bone age, and height standard deviation score (Ht-SDS). In children with the homozygous pathological genotype, a strong inverse relationship between IGF-1 and Ht-SDS was detected. Biochemical blood parameters, including calcium, phosphorus, creatinine, urea, and cholesterol, did not differ significantly between genotype groups and remained within normal reference ranges. Regression analysis confirmed a significant influence of bone age on IGF-1 and stimulated GH levels, as well as a close association between IGF-1 and stimulated GH. Analysis of VDR genotypes demonstrated that the GATCAC combination was the most prevalent among children with GHD (55.56%). These findings highlight the substantial contribution of genetic factors to the pathogenesis of GHD and support the feasibility of personalized diagnostic and therapeutic approaches.