THU398 Variants In The Vitamin D Receptor, 1alpha-hydroxylase Enzyme Genes In Cholecalciferol Therapy

Disclosure: S. Kalinchenko: None. L. Vorslov: None. T. Shkeleva: None. A. Kahn: None. O. Samburskaya: None. The administration of vitamin D drugs should be done with regard to genetic analysis of polymorphisms in the vitamin D receptor (VDR) and 1alpha-hydroxylase enzyme (CYP27B1) genes to select the required dose, form and activity of the drug. Materials and Methods: In the period from 10.10.2020 to 23.12.2022 there were 936 patients aged from 2 to 77 years on therapy with cholecalciferol, in whom vitamin D status was determined by calcidiol mass spectrometry and parathormone in blood. Patients were genotyped for two markers of susceptibility to vitamin D deficiency: variants in the vitamin D receptor gene (VDR, BsmI Polymorphism, rs1544410) and the 1-alpha hydroxylase enzyme gene (CYP27B1, g.57764205A>G; rs4646536) by direct sequencing. Findings: Patients received therapy with cholecalciferol preparations. As a result, they were divided into 2 groups: the first group in which clinical effects of vitamin D deficiency compensation were achieved against the background of treatment, the second group in which, despite taking adequate selected doses, considering age, weight and degree of deficiency, laboratory criteria of vitamin D sufficiency were achieved, but clinical effects were not achieved. Genetic analysis showed that those patients in whom clinical symptoms of vitamin D deficiency were more severe and those in whom therapy with cholecalciferol did not produce the expected clinical effect had polymorphisms in the genes encoding VDR and/or 1alpha-hydroxylase enzyme. Discussion: In the presence of the CYP27B1 variant, g.57764205A>G; rs4646536 in the gene encoding 1alpha-hydroxylase (86.5% of all patients, n = 809), calcitriol formation is reduced, which explains the lack of effect of cholecalciferol therapy. In the presence of the VDR variant, BsmI Polymorphism, rs1544410 in the gene encoding the vitamin D receptor, sensitivity of the receptor to hormone D is reduced (13% of all patients, n = 122), which explains the lack of clinical effects of therapy with vitamin D drugs in standard therapeutic doses. And the most difficult to treat clinical manifestations of vitamin D deficiency occur in patients with polymorphisms in the two genes encoding both VDR and 1alpha-hydroxylase, which constituted 11.3% (n = 106) according to our study among all those examined. Conclusion: Conflicting literature data and clinical effects in vitamin D therapy are due to variants in the VDR and/or CYP27B1 genes. Knowledge of genetics is the individualized dose, form, and activity of vitamin D medication as the key to success in therapy. Presentation: Thursday, June 15, 2023