medalphabetМедицинский алфавитMedical alphabet2078-56312949-2807ООО «Альфмед»10.33667/2078-5631-2023-14-18-21medalphabet-3243Research ArticleСтатьиСвязь особенностей течения рассеянного склероза с полиморфизмами гена рецептора кальцитриола VDR FokI (rs2228570), BSMI (rs1544410), TaqI (rs731236), ApaI (rs7975232)Association between course of multiple sclerosis and polymorphisms of calcitriol receptor gene VDR FokI (rs2228570), BSMI (rs1544410), TaqI (rs731236), ApaI (rs7975232)https://orcid.org/0000-0002-1875-3890ЛуневК. В.LunevK. V.

Лунев Константин Валерьевич - врач-невролог, ассистент кафедры неврологии и нейрохирургии с курсом ДПО.

Барнаул

Konstantin V. Lunev - neurologist, assistant at Dept of neurology and neurosurgery.

Barnaul

lunev-k@mail.ruФГБОУ ВО «Алтайский государственный медицинский университет» Минздрава РоссииРоссияAltai State Medical UniversityRussian Federation202319102023014«Неврология и психиатрия» (2)1821Copyright © Лунев К.В., 20232023Лунев К.В.Lunev K.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-alphabet.com/jour/article/view/3243Цель

Цель. Оценить связь частоты обострений и темпов прогрессирования рассеянного склероза (РС) с полиморфизмами гена рецептора кальцитриола VDR FokI (rs2228570), BSMI (rs1544410), TaqI (rs731236), ApaI (rs7975232).

Материал и методы

Материал и методы. В исследовании приняли участие 90 больных c ремиттирующим течением РС. Все пациенты – европеоиды, родились и проживали в Алтайском крае Российской Федерации. Генотипирование проводили методом TaqMan-зондов.

Результаты

Результаты. Обнаружен протективный эффект TT генотипа VDR FokI (rs2228570) в отношении риска нарастания инвалидизации более 0,75 балла в год по расширенной шкале инвалидизации (р = 0,034). Выявлен также протективный эффект ТT генотипа полиморфизма TaqI (rs731236) относительно обострений РС чаще раза в год (р = 0,041). Не найдено ассоциаций особенностей течения РС с другими исследованными полиморфизмами.

Заключение

Заключение. Можно полагать, что полиморфизмы VDR FokI (rs2228570) и TaqI (rs731236) могут влиять на течение ремитирующего РС. Механизмы этих влияний могут включать модуляцию иммунно-воспалительных реакций в центральной нервной системе, являющихся ключевым звеном патогенеза РС.

Objective

Objective. To evaluate the relationship between the frequency of exacerbations and the rate of progression of multiple sclerosis (MS) and polymorphisms of the calcitriol receptor gene VDR FokI (rs2228570), BSMI (rs1544410), TaqI (rs731236), ApaI (rs7975232).

Material and methods

Material and methods. Ninety patients with relapsing-remitting MS took part in the study. All patients are Caucasians, were born and lived in the Altai region of the Russian Federation. Genotyping was performed by TaqMan probes.

Results

Results. A protective effect of the TT genotype VDR FokI (rs2228570) on the risk of increasing disability of more than 0.75 points per year according to the expanded disability scale was found (p = 0.034). The protective effect of the TT genotype of the TaqI polymorphism (rs731236) on exacerbations of MS more than once a year (p = 0.041) was also revealed. Associations of the MS course with other studied polymorphisms were not found.

Conclusions

Conclusions. It can be assumed that the VDR FokI (rs2228570) and TaqI (rs731236) polymorphisms may influence the course of relapsing-remitting MS. The mechanisms of these influences may include the modulation of immune-inflammatory responses in the central nervous system, which are a key link in the MS pathogenesis.

рассеянный склерозвитамин DVDR FokI (rs2228570)BSMI (rs1544410)TaqI (rs731236)ApaI (rs7975232)multiple sclerosisvitamin DVDR FokI (rs2228570)BSMI (rs1544410)TaqI (rs731236)ApaI (rs7975232)ReferencesБойко А. Н., Гусев Е. И. Современные алгоритмы диагностики и лечения рассеянного склероза, основанные на индивидуальной оценке состояния пациента. Журнал неврологии и психиатрии им. С. С. Корсакова. 2017; (2–2): 92–106. https://doi.org/10.17116/jnevro20171172292–106Boyko A. N., Gusev E. I. Current algorithms of diagnosis and treatment of multiple sclerosis based on the individual assessment of the patient. Journal of Neurology and Psychiatry n.a. S.S. Korsakov. 2017; (2–2): 92–106. https://doi.org/10.17116/jnevro20171172292–106Скоромец А. А., Тотолян Н. А., Барбас И. М. Рассеянный склероз: критерии диагноза и современная терапия. Новые Санкт-Петербургские врачебные ведомости. 2005; (3): 66–76.Skoromets A.A., Totolyan N.A., Barbas I.M. Multiple sclerosis: Diagnostic criteria and modern therapy. New St. Petersburg Medical Gazette. 2005; (3): 66–76.Шмидт Т.Е, Яхно Н. Н. Рассеянный склероз: руководство для врачей. М.: МЕДпресс-информ, 5-е изд. 2016; 272.Schmidt T.E, Yakhno N. N. Multiple sclerosis: A guide for doctors. Moscow: MEDpress-inform, 5th ed. 2016; 272.Рассеянный склероз. Клинические рекомендации. Всероссийское общество неврологов; Национальное общество нейрорадиологов; Медицинская ассоциация врачей и центров рассеянного склероза и других нейроиммуно-логических заболеваний; Российский комитет исследователей рассеянного склероза. М., 2022. Дата размещения: 13.07.2022. ID:739. URL: https://diseases. medelement.com/disease/рассеянный-склероз-кр-рф-2022/17221Multiple sclerosis. Clinical guidelines. All-Russian Society of Neurologists; National Society of Neuroradiology; Medical Association of Physicians and Centers for Multiple Sclerosis and Other Neuroimmunological Diseases; Russian committee of researchers of multiple sclerosis. M., 2022. Placement date: 07/13/2022. ID:739. URL: https://diseases.medelement.com/disease/multiple-sclerosis-cr-rf-2022/17221Miclea A. A., Bagnoud M., Chan A., Hoepner R. Brief Review of the Effects of Vitamin D on Multiple Sclerosis. Front Immunol. 2020; (11): 781. https://doi.org/10.3389/fimmu.2020.00781Miclea A. A., Bagnoud M., Chan A., Hoepner R. Brief Review of the Effects of Vitamin D on Multiple Sclerosis. Front Immunol. 2020; (11): 781. https://doi.org/10.3389/fimmu.2020.00781Zahoor I. S., Haq E. Vitamin D and Multiple Sclerosis: An Update Multiple Sclerosis: Perspectives in Treatment and Pathogenesis. Brisbane (AU): Codon Publications. 2017; Chapter 5. https://doi.org/15586/codon.multiplesclerosis.2017.ch5Zahoor I. S., Haq E. Vitamin D and Multiple Sclerosis: An Update Multiple Sclerosis: Perspectives in Treatment and Pathogenesis. Brisbane (AU): Codon Publications. 2017; Chapter 5. https://doi.org/15586/codon.multiplesclerosis.2017.ch5Mei I., Ponsonby A. L., Dwyer T. et al. Vitamin D levels in people with multiple sclerosis and community controls in Tasmania, Australia. J Neurol. 2007; (254): 581–590. https://doi.org/10.1007/s00415–006–0315–8Mei I., Ponsonby A. L., Dwyer T. et al. Vitamin D levels in people with multiple sclerosis and community controls in Tasmania, Australia. J Neurol. 2007; (254): 581–590. https://doi.org/10.1007/s00415–006–0315–8Cui X., Gooch H., Petty A. et al. Vitamin D and the brain: Genomic and nongenomic actions. Mol Cell Endocrinol. 2017; (453): 131–143. https://doi.org/10.1016/j.mce.2017.05.035Cui X., Gooch H., Petty A. et al. Vitamin D and the brain: Genomic and nongenomic actions. Mol Cell Endocrinol. 2017; (453): 131–143. https://doi.org/10.1016/j.mce.2017.05.035Dankers W., Colin E. M., van Hamburg J. P., Lubberts E. Vitamin D in Autoimmunity: Molecular Mechanisms and Therapeutic Potential. Front Immunol. 2017; (7): 697. https://doi.org/10.3389/fimmu.2016.00697Dankers W., Colin E. M., van Hamburg J. P., Lubberts E. Vitamin D in Autoimmunity: Molecular Mechanisms and Therapeutic Potential. Front Immunol. 2017; (7): 697. https://doi.org/10.3389/fimmu.2016.00697Walsh J.S., Bowles S., Evans A.L. Vitamin D in obesity. Curr Opin Endocrinol Diabetes Obes. 2017; (6): 389–394. https://doi.org/10.1097/MED.0000000000000371Walsh J.S., Bowles S., Evans A.L. Vitamin D in obesity. Curr Opin Endocrinol Diabetes Obes. 2017; (6): 389–394. https://doi.org/10.1097/MED.0000000000000371Ruiz-Ballesteros A.I., Meza-Meza M.R., Vizmanos-Lamotte B., et al. Association of Vitamin D Metabolism Gene Polymorphisms with Autoimmunity: Evidence in Population Genetic Studies. Int J Mol Sci. 2020; (24): 9626. https://doi.org/10.3390/ijms21249626Ruiz-Ballesteros A.I., Meza-Meza M.R., Vizmanos-Lamotte B., et al. Association of Vitamin D Metabolism Gene Polymorphisms with Autoimmunity: Evidence in Population Genetic Studies. Int J Mol Sci. 2020; (24): 9626. https://doi.org/10.3390/ijms21249626Polman C. H., Reingold S. C., Banwell B., et al. Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteria. Annals of neurology. 2011; (2): 292–302. https://doi.org/10.1002/ana.22366Polman C. H., Reingold S. C., Banwell B., et al. Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteria. Annals of neurology. 2011; (2): 292–302. https://doi.org/10.1002/ana.22366Kurtzke J. F. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983; (11): 1444–1452. https://doi.org/10.1212/wnl.33.11.1444Kurtzke J. F. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983; (11): 1444–1452. https://doi.org/10.1212/wnl.33.11.1444Agliardi C., Guerini F. R., Saresella M., et al. Vitamin D receptor (VDR) gene SNPs influence VDR expression and modulate protection from multiple sclerosis in HLA-DRB 1*15-positive individuals. Brain, behavior, and immunity. 2011; (7): 1460–1467. https://doi.org/10.1016/j.bbi.2011.05.015Agliardi C., Guerini F. R., Saresella M., et al. Vitamin D receptor (VDR) gene SNPs influence VDR expression and modulate protection from multiple sclerosis in HLA-DRB 1*15-positive individuals. Brain, behavior, and immunity. 2011; (7): 1460–1467. https://doi.org/10.1016/j.bbi.2011.05.015Niino M., Fukazawa T., Yabe I., et al. Vitamin D receptor gene polymorphism in multiple sclerosis and the association with HLA class II alleles. J. Neurol. Sci. 2000; (177/1): 65–71. https://doi.org/10.1016/s0022–510x(00)00336–1Niino M., Fukazawa T., Yabe I., et al. Vitamin D receptor gene polymorphism in multiple sclerosis and the association with HLA class II alleles. J. Neurol. Sci. 2000; (177/1): 65–71. https://doi.org/10.1016/s0022–510x(00)00336–1Křenek P., Benešová Y, Bienertová-Vašků J, Vašků J. The Impact of Five VDR Polymorphisms on Multiple Sclerosis Risk and Progression: A Case-Control and Genotype-Phenotype Study. J Mol Neurosci. 2018; 64 (4): 559–566. Doi: 10.1007/s12031–018–1034–1.Křenek P., Benešová Y, Bienertová-Vašků J, Vašků J. The Impact of Five VDR Polymorphisms on Multiple Sclerosis Risk and Progression: A Case-Control and Genotype-Phenotype Study. J Mol Neurosci. 2018; 64 (4): 559–566. Doi: 10.1007/s12031–018–1034–1.Lu M., Taylor B. V., Körner H. Genomic Effects of the Vitamin D Receptor: Potentially the Link between Vitamin D, Immune Cells, and Multiple Sclerosis. Front Immunol. 2018; (9): 477. https://doi.org/10.3389/fimmu.2018.00477Lu M., Taylor B. V., Körner H. Genomic Effects of the Vitamin D Receptor: Potentially the Link between Vitamin D, Immune Cells, and Multiple Sclerosis. Front Immunol. 2018; (9): 477. https://doi.org/10.3389/fimmu.2018.00477de Abreu D. A.F., Eyles D., Feron F. Vitamin D, aneuro-immunomodulator: Implications for neurodegenerative and autoimmune diseases. Psychoneuroendocrinology. 2009; (Vol. 34, Suppl 1): 265–277. https://doi.org/10.1016/j.psyneuen.2009.05.023de Abreu D. A.F., Eyles D., Feron F. Vitamin D, aneuro-immunomodulator: Implications for neurodegenerative and autoimmune diseases. Psychoneuroendocrinology. 2009; (Vol. 34, Suppl 1): 265–277. https://doi.org/10.1016/j.psyneuen.2009.05.023Smolders J., Thewissen M., Peelen E et al. Vitamin D status is positively correlated with regulatory T cell function in patients with multiple sclerosis. PLoS One. 2009; (Vol. 4, No. 8): e6635. https://doi.org/10.1371/journal.pone.0006635Smolders J., Thewissen M., Peelen E et al. Vitamin D status is positively correlated with regulatory T cell function in patients with multiple sclerosis. PLoS One. 2009; (Vol. 4, No. 8): e6635. https://doi.org/10.1371/journal.pone.0006635Disanto G., Morahan J.M., Barnett M.H. et al. The evidence for a role of B cells in multiple sclerosis. Neurology. 2012; (Vol. 78, No. 11): 823–832. https://doi.org/10.1212/WNL.0b013e318249f6f0Disanto G., Morahan J.M., Barnett M.H. et al. The evidence for a role of B cells in multiple sclerosis. Neurology. 2012; (Vol. 78, No. 11): 823–832. https://doi.org/10.1212/WNL.0b013e318249f6f0Jahromi S. R., Sahraian M. A. et al. Iranian consensus on use of vitamin D in patients with multiple sclerosis. BMC Neurol. 2016; (16): 76. https://doi.org/10.1186/s12883–016–0586–3Jahromi S. R., Sahraian M. A. et al. Iranian consensus on use of vitamin D in patients with multiple sclerosis. BMC Neurol. 2016; (16): 76. https://doi.org/10.1186/s12883–016–0586–3

The authors declare that there are no conflicts of interest present.