Abstract
Abstract. Vitamin D (Vit. D) and its receptor gene (VDR) are essential for human health, because they regulate the expression of genes involved
in calcium homeostasis, energy metabolism, cell growth and differentiation, and immune processes. Vit. D and four single nucleotide polymorphisms of the VDR gene, ApaI, BsmI, TaqI, and FokI, are able to directly influence critical genes responsible for insulin secretion and its activity, which can contribute to the development of insulin resistance (ІR), type 2 diabetes, and other metabolic conditions. In Ukraine, no studies have been conducted on the relationship between the VDR BsmI gene polymorphism and the content of Vit. D and IR in the pediatric population.
Aim: to investigate the serum 25-hydroxyvitamin D (25(ОН) D) content and assess the risk of developing insulin resistance in adolescents with hypothalamic dysfunction depending on the VDR BsmI gene polymorphism variants (rs1544410).
Material and methods. A total of 35 adolescents (23 boys, 65.71%) with hypothalamic dysfunction (DH) were examined. The 25(ОН)D content was determined in patients by mmunochemiluminescence method insulin, glycated hemoglobin in the blood serum, HOMA-IR index, body mass index (BMI), and the distribution of allele frequencies of the VDR BsmI gene polymorphism (rs1544410) in children with DH were also studied by polymerase chain reaction with subsequent analysis of the length of restriction fragments when they were detected by agarose gel electrophoresis.
Results. Patients were divided into two groups: group 1 – 22 persons (62.65%) – carriers of the GA genotype of the VDR BsmI gene polymorphism (rs1544410); group II – 12 persons (34.29%) – had the GG genotype. Only one boy (2.86%) had the AA genotype and was not included in any group. The average age, height, glycated hemoglobin and blood insulin were within the reference values and practically did not differ between patients with the GA and GG genotypes. The BM and BMI indicators in patients corresponded to obesity of varying degrees. BMI on average was 33.07±1.51 kg/m2 and 32.36±1.51 kg/m2 in groups I and II, respectively, and did not differ significantly (p=0.741764). The average HOMA-IR index in general for the groups exceeded the limit values for people with obesity - in patients of group I this indicator was 4.79±0.76, in patients of group II - 3.71±0.54, which indicates the presence of IR in both groups, slightly higher in adolescents with the AG genotype of the VDR BsmI gene polymorphism (rs1544410). The serum 25(OH) D in both groups corresponded to the degree of severe vit. D deficiency. In patients of group I, the 25(OH)D level was 33.03±3.64 nmol/l, and was significantly lower than in patients of group II (53.23±7.16, p=0.017306). In the groups of patients examined by us, the GA BsmI VDR genotype dominated, which was associated with the lowest level of serum 25(OH)D. In the group of patients, heterozygotes GA (62.85%) prevailed, and in the control group, homozygotes GG (66.00%). In patients with DH and IR and in the presence of the
GG genotype, the risk of developing this pathology was significantly reduced, OR=0.27 (95%CI 0.11-0.68; p<0.005); in the presence of the
heterozygous GA polymorphism, the risk is significantly high OR=5.54 (95%CI 2.12-14.49; p<0.0005). Conclusions. In patients with DH and the presence of the GA BsmI (rs1544410) polymorphism of the VDR gene, a severe deficiency of vitamin D was found. The presence of the GA BsmI (rs1544410) VDR genotype significantly increases the risk of developing IR in adolescents with DH, regardless of gender. The combination of such indicators as vitamin D deficiency, elevated HOMAIR index, and heterozygous BsmI polymorphism (rs1544410) of the VDR gene in adolescents with DH is the rationale for including such patients in the high-risk group for developing critical cardiometabolic conditions.
References
Zhumina AG, Li K, Konovalova AA, Li YA, Ishmuratova MY, Pogossyan GP, et al. Plasma 25-hydroxyvitamin D levels and VDR gene expression in peripheral blood mononuclear cells of leukemia patients and healthy subjects in Central Kazakhstan. Nutrients. 2020 Apr 26;12(5):1229. doi: 10.3390/nu12051229.
Agliardi C, Guerini FR, Bolognesi E, Zanzottera M, Clerici M. VDR gene single nucleotide polymorphisms and autoimmunity: a narrative review. Biology (Basel). 2023 Jun 26;12(7):916. doi: 10.3390/biology12070916.
Chiu KC, Chu A, Go VL, Saad MF. Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Am J Clin Nutr. 2004 May;79(5):820-5. doi: 10.1093/ajcn/79.5.820.
Contreras-Bolívar V., García-Fontana B., García-Fontana C., Muñoz-Torres M. Mechanisms involved in the relationship between vitamin D and insulin resistance: impact on clinical practice. Nutrients. 2021 Oct 1; 13(10):3491. doi: 10.3390/nu13103491.
Klashami ZN, Ahrabi NZ, Ahrabi YS, Hasanzad M, Asadi M, Amoli MM. The vitamin D receptor gene variants, ApaI, TaqI, BsmI, and FokI in diabetic foot ulcer and their association with oxidative stress. Mol Biol Rep. 2022 Sep;49(9):8627-8639. doi: 10.1007/s11033-022-07698-2.
International Diabetes Federation. Global IDF/ISPAD guideline for diabetes in childhood and adolescence [accessed on 15 January 2015]. Available online: http://www.idf.org/sites/default/files/Diabetes-in-Childhood-and-Adolescence-Guidelines.pdf
Śledzińska K, Kloska A, Jakóbkiewicz-Banecka J, Landowski P, Oppmann A, Wilczynski S, et al. The role of vitamin D and vitamin D receptor gene polymorphisms in the course of inflammatory bowel disease in children. Nutrients. 2024 Jul 13;16(14):2261. doi: 10.3390/nu16142261.
World Health Organization. WHO child growth standards: length/height-for-age, etweight-for-age, weight-for-length, weight-for height and bodymass index-for-age: methods and development. Genewa: WHO Press; 2017. 312 p.
Ströhle A. Die aktuellen empfehlungen des US-amerikanischen Institute of Medicine (IOM) für die vitamin-D-zufuhr. Eine kritische würdigung [The updated recommendations of the US Institute of Medicine (IOM) on the intake of vitamin D. A critical appraisal]. Med Monatsschr Pharm. 2011 Aug;34(8):291-8. German.
Fletcher D, Faddy M. Confidence intervals for expected a bundance of rare species. JABES. 2007;12:315-24. doi: 10.1198/108571107X229322.