M.A. BUKHALKO¹, E.Yu. SKRIPCHENKO^1, 2, N.V. SKRIPCHENKO^1, 2, L.A. ALEKSEEVA¹, S.G. GRIGORIEV^{1, 3}

¹Pediatric Research and Clinical Center for Infectious Diseases, Saint Petersburg

²Saint Petersburg State Pediatric Medical University, Ministry of Healthcare of the Russian Federation, Saint Petersburg

³S.M. Kirov Military Medical Academy, Ministry of Defense of the Russian Federation, Saint Petersburg

  Contact details:

Bukhalko M.A. — post-graduate student of the Department of Neuroinfections and Organic Pathology of the nervous system 

Address: 9 Professor Popov St., Saint Petersburg, Russian Federation, 197022, tel. +7-965-041-96-60, e-mail: marinabuhalko@mail.ru

Inflammatory diseases of сentral nervous system have a leading position in the frequency of disabling effects and mortality in children. Specific features of the course of these diseases can be genetically determined.

The purpose — to identify the relationship between BsmI polymorphism of vitamin D receptor gene and the course of inflammatory diseases of central nervous system.

Material and methods. There were examined whole blood samples of 107 children (34 — with encephalitis, 28 — with disseminated encephalomyelitis, 20 — with multiple sclerosis, 25 — comparison group). Determination of BsmI genotypes of vitamin D receptor gene polymorphism was carried out by polymerase chain reaction followed by restriction analysis (DNA reagent kit Technology).

Results. The distribution of AA, AG and GG genotypes and the occurrence of A and G alleles of BsmI polymorphism of vitamin D receptor gene did not differ significantly in the study population and the comparison group. However, an extremely severe course of encephalitis and recurrent exacerbations of disseminated encephalomyelitis and multiple sclerosis in the early period of the onset of the disease were significantly more often observed in carriers of GG genotype and allele G of this polymorphism.

Conclusion. Our results showed that GG genotype and allele G BsmI polymorphism of vitamin D receptor gene in children with inflammatory diseases of central nervous system might possibly be an unconventional risk factor for the adverse course of the disease.

Key words: encephalitis, disseminated encephalomyelitis, multiple sclerosis, vitamin D, inflammation, polymorphism of vitamin D receptor gene.

(For citation: Bukhalko M.A., Skripchenko E.Yu., Skripchenko N.V., Alekseeva L.A., Grigoriev S.G. Role of BsmI polymorphism of vitamin D receptor gene in the pathogenesis of inflammatory diseases of central nervous system in children. Practical medicine. 2019. Vol. 17, № 5, P. 170-174)

REFERENCES

1. Gromova O.A., Torshin I.Yu. Vitamin D – smena paradigm [Vitamin D — a paradigm shift]. Moscow: GEOTAR-Media, 2017. 576 p.
2. Skripchenko N.V., Ivanova G.P., Skripchenko E.Yu., Surovtseva A.V. Demieliniziruyushchie zabolevaniya nervnoy sistemy u detey: etiologiya, klinika, patogenez, diagnostika, lechenie [Demyelinating diseases of the nervous system in children: etiology, clinical features, pathogenesis, diagnosis, treatment]. Moscow: Kommentariy, 2016. 352 p.
3. Skripchenko E.Yu. Kliniko-patogeneticheskie determinanty differentsial’noy diagnostiki entsefalitov, disseminirovannykh entsefalomielitov i rasseyannogo skleroza u detey: avtoref. dokt. diss. [Clinical and pathogenetic determinants of the differential diagnosis of encephalitis, disseminated encephalomyelitis and multiple sclerosis in children. Synopsis of Dr’s dis.]. Saint Petersburg, 2018. 43 p.
4. Krupp L.B., Tardieu M., Amato M.P., Banwell B., Chitnis T., Dale R.C. et al. International Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: revisions to the 2007 definitions. Multiple Sclerosis Journal, 2013, vol. 0 (0), pp. 1–7.
5. Pludowski P, Holick M.F., Pilz S., Wagner C.L., Hollis B.W., Grant W.B. et al. Vitamin D effects on musculoskeletal health, immunity, autoimmunity, cardiovascular disease, cancer, fertility, pregnancy, dementia and mortality-a review of recent evidence. Autoimmun Rev, 2013, vol. 12 (10), pp. 976–989.
6. Huhtakangas J.A., Olivera C.J., Bishop J.E., Zanello L.P., Norman A.W. The vitamin D receptor is present in caveolae-enriched plasma membranes and binds 1,25(OH)2-vitamin D3 in vivo and in vitro. Mol Endocrinol, 2004, vol. 18 (11), pp. 2660-2671.
7. Zhao G., Simpson R. U. Membrane localization, Caveolin-3 association and rapid actions of vitamin D receptor in cardiac myocytes. Steroids, 2010, vol. 75 (8–9), pp. 555–559.
8. Kostik M.M., Shcheplyagina L.A., Larionova V.I. The role of the genetic polymorphism of the vitamin D receptor gene (VDR) in the pathogenesis of juvenile idiopathic arthritis: theoretical and practical aspects. Sovr. revmatologiya, 2014, vol. 3, pp. 28–33 (in Russ.).
9. Myslivets M.G., Paramonova N.S., Stepuro T.L. The role of vitamin D receptor gene polymorphism in the pathogenesis of juvenile rheumatoid arthritis. Meditsinskie novosti, 2017, vol. 9, pp. 72–74 (in Russ.).
10. Bukhalko M.A., Skripchenko E.Yu., Alekseeva L.A., Skripchenko N.V., Monakhova N.E., Grigor’ev S.G. Vitamin D and neurospecific proteins in children with inflammatory-demyelinating diseases of the central nervous system: causes and effects. Pediatr, 2019, vol. 10 (3), pp. 17–24 (in Russ.).
11. Bukhalko M.A., Skripchenko N.V., Skripchenko E.Yu., Imyanitov E.N. The value of polymorphism of the vitamin D receptor gene in human pathology. Rossiyskiy vestnik perinatologii i pediatrii, 2017, vol. 62 (6), pp. 23–28 (in Russ.).
12. Areeshi M.Y., Mandal R.K., Dar S.A., Alshahrani A.M., Ahmad A., Jawed A. et al. A reappraised meta-analysis of the genetic association between vitamin D receptor BsmI (rs1544410) polymorphism and pulmonary tuberculosis risk. Biosci Rep, 2017, vol. 37 (3).
13. Bermúdez-Morales V.H., Fierros G., Lopez R.L., Martínez-Nava G., Flores-Aldana M., Flores-Rivera J. et al. Vitamin D receptor gene polymorphisms are associated with multiple sclerosis in Mexican adults. J Neuroimmunol, 2017, vol. 306, pp. 20–24.
14. Bettencourt A., Boleixa D., Guimarães A.L., Leal B., Carvalho C., Brás S. et al. The vitamin D receptor gene FokI polymorphism and Multiple Sclerosis in a Northern Portuguese population. J Neuroimmunol, 2017, vol. 309, pp. 34–37.
15. Despotovic M., Jevtovic Stoimenov T., Stankovic I., Basic J., Pavlovic D. Vitamin D Receptor Gene Polymorphismsin Serbian Patients With Bronchial Asthma: A Case-Control Study. J Cell Biochem, 2017, vol. 118 (11), pp. 3986–3992.
16. Iordanidou M., Paraskakis E., Giannakopoulou E., Tavridou A., Gentile G., Borro M., Simmaco M. et al. Vitamin D receptor ApaI a allele is associated with better childhood asthma control and improvement in ability for daily activities. OMICS, 2014, vol. 18 (11), pp. 673–681.
17. Temaimi R.A., Enezi A., Serri A., Roughani R., Mulla F. The Association of Vitamin D Receptor Polymorphisms with Multiple Sclerosis in a Case-Control Study from Kuwait. PLOS ONE, 2015, vol. 10 (11), p. e0142265.
18. Xia S., Lin X., Guo M., Jiang L., Jin J., Lin X. et al. An analysis of vitamin D receptor gene polymorphisms and serum 25-hydroxyvitamin D levels in patients with Crohn’s disease. Nei Ke Za Zhi, 2015, vol. 54 (7), pp. 601–606.
19. Xia S., Xia X., Wang W., Yu L., Jin J., Lin X. et al. Associations of ulcerative colitis with vitamin D receptor gene polymorphisms and serum levels of 25-hydroxyl vitamin D. Zhonghua Yi Xue Za Zhi, 2014, vol. 94 (14), pp. 1060–1066.
20. Uitterlinden A.G., Fang Y., van Meurs J.B.J., Pols H.A.P., van Leeuwen J.P.T.M. Genetics and biology of vitamin D receptor polymorphisms. Review. Gene, 2004, vol. 338, pp. 143–156.
21. Gordon-Lipkin E., Banwell B. An update on multiple sclerosis in children: diagnosis, therapies, and prospects for the future. Expert Review of Clinical Immunology, 2017, vol. 42.