Polymorphism of the organic anion transporter protein 1B1 OATP1B1 rs2306283 gene in children with thyroid diseases living in the Far North

Abstract

The increased prevalence of iodine deficiency diseases, such as thyroid pathology, is an extremely urgent problem for Russia. Huge part of the country's territory, including the Extreme North regions, is situated in the iodine deficiency zone. Iodine deficiency diseases of the thyroid gland are widespread among prepubescent children living in this area. Polymorphism of thyroid hormone transporter genes, including the organic anion transporter 1B1 protein OATP1B1 gene is associated with changes in their functional activity. It causes the thyroid pathologies development in children living in the conditions of iodine deficiency in the Far North. The aim of the work is to study the polymorphism of the organic anion transporter protein 1B1 OATP1B1 rs2306283 gene associated with the changes of endocrine regulation in living in the Far North children with thyroid diseases. Materials and methods. A clinical and laboratory examination of children living in conditions of iodine deficiency in the Far North was conducted. The observation group consists of 52 children with thyroid diseases (congenital iodine deficiency syndrome, hypothyroidism, thyroid disease, endemic goiter). The comparison group includes 54 children without pathologies of the endocrine system. The iodine content in urine was determined by a unified method using spectrophotometry. The thyroid-stimulating hormone (TSH) level was determined by enzyme immunoassay. The SNP of the OATP1B1 gene (rs2306283) was identified using the real-time PCR technique. Results. The results of the clinical and laboratory biological media analysis in the examined children demonstrate a reduced iodine content in the urine of children with thyroid pathology relative to the comparison group and the reference level (p<0.05). At the same time, the level of thyroid-stimulating hormone exceeds similar values in the comparison group (p<0.05). Polymorphism of the organic anion transporter 1B1 protein OATP1B1 (rs2306283) gene in children with thyroid diseases is characterized by the increased C-allele frequency relative to the comparison group (OR=1.79 (CI: 1.03-3.09); р<0.05). It may be associated with thyroid hormone transport inhibition. Conclusion. Thus, the endocrine profile of children with established thyroid pathology living in conditions of iodine deficiency in the Far North is characterized by an imbalance of the pituitary-thyroid system according to the criterion of an increase in TSH content against the background of a decrease in iodine content in urine (p<0.05), which indicates a decrease in the functional activity of the thyroid gland. The established increased C-allele frequency of the OATP1B1 gene (rs2306283) indicates the formation of pathogenetic trends in the transport of thyroid hormones in the presence of thyroid diseases in conditions of natural iodine deficiency. Genotyping of the OATP1B1 gene (rs2306283) polymorphic markers associated with excessive TSH levels against the background of iodine deficiency in biological media can be used for prevention, early diagnosis and personal therapy of thyroid diseases in the population of iodine-deficient territories.