Assessment of the prevalence of polymorphisms in genes encoding the vitamin D receptor and the 1α-hydroxylase enzyme in residents of Moscow and the Moscow Region for personalized treatment regimen with vitamin D preparations
Authors:   Patrice Lumumba Peoples’ Friendship University of Russia (RUDN), Moscow, Russian Federation, Kalinchenko S.Yu. ,   Professor Kalinchenko Clinic, Moscow, Russian Federation, Samburskaya O.V. ,   Patrice Lumumba Peoples’ Friendship University of Russia (RUDN), Moscow, Russian Federation,   Professor Kalinchenko Clinic, Moscow, Russian Federation, Napolsky I.N. ,   Nautilus Health Care Centre, Saint Petersburg, Russian Federation, Shkeleva T.A. ,   “Allel” LLC, Moscow, Russian Federation, Vorslov L.O. ,   Patrice Lumumba Peoples’ Friendship University of Russia (RUDN), Moscow, Russian Federation,   Professor Kalinchenko Clinic, Moscow, Russian Federation
Published: September 2024

The use of vitamin D preparations in the treatment of several diseases is of great interest, given its multiple and diverse effects. However, despite the positive experience with cholecalciferol, there are patients in whom clinical efficacy is either absent or poorly expressed, and similar data are available in published studies. Polymorphisms in genes encoding the vitamin D receptor and the 1α-hydroxylase enzyme are a necessary addition to laboratory parameters to allow proper selection of the dose, regimen, form, and chemical structure of the vitamin D preparation. Objective. To assess the prevalence of polymorphisms in genes encoding the vitamin D receptor and the 1α-hydroxylase enzyme in residents of Moscow and the Moscow Region. Patients and methods. The study included 3000 patients living in Moscow and the Moscow Region, aged 2 to 77 years, treated with vitamin D preparations in Professor Kalinchenko Clinic between October 10, 2020, and December 23, 2023. Patients were genotyped by direct sequencing for two markers of susceptibility to vitamin D deficiency: variants in the vitamin D receptor gene (VDR, BsmI Polymorphism, rs1544410) and the 1α-hydroxylase enzyme gene (CYP27B1, g.57764205A>G; rs464656536). Statistical data processing was performed using IBM SPSS Statistics 23.0 software (USA). Results. Polymorphism in the gene encoding the 1α-hydroxylase enzyme was detected in 2595 (89.5%) of 3000 patients, of which heterozygotes (A/G) in 1434 (47.8%) and homozygotes (A/A) in 1161 (38.7%). Polymorphism in the gene encoding VDR was detected in 429 (14.3%) patients, of which heterozygotes (C/T) in 1338 (44.6%) and homozygotes (C/C) in 1233 (41.1%). The combination of polymorphisms in the CYP27B1 and VDR genes was detected in 375 (12.5%) patients, the absence of polymorphisms in two genes – in 351 (11.7%). Discussion. In the presence of CYP27B1, g.57764205A > G; rs4646536 in the gene encoding the 1α-hydroxylase enzyme, the intensity of calcitriol formation is reduced, which explains the lack of effect of therapy with cholecalciferol preparations. In the presence of VDR, BsmI Polymorphism, rs1544410 in the gene encoding the vitamin D receptor, the sensitivity of the receptor to hormone D is reduced, which explains the lack of clinical effects of therapy with vitamin D preparations in standard therapeutic doses. The most difficult-to-treat clinical manifestations of vitamin D deficiency were found in patients with polymorphisms in two genes encoding both VDR and 1α-hydroxylase, which amounted to 12.5% (375 people) of the total number of patients; among all patients examined, only 351 (11.7%) did not have polymorphisms in these two genes. Conclusion. Controversial literature data and clinical effects of vitamin D therapy are due to variants in the VDR and/or CYP27B1 genes. Knowledge of genetics allows individualization of the dose, form, and chemical activity of the vitamin D preparation, which is the key to success of therapy. Key words: vitamin D, calcidiol, calcitriol, vitamin D receptor, cholecalciferol, 1α-hydroxylase