Zastupljenost polimorfizama BsmI i FokI gena za vitamin D receptor kod pacijenata sa multiplom sklerozom u Srbiji

  • Lazar Bajić Klinika za neurologiju, Univerzitetski Klinički centar Niš, Niš, Republika Srbija
  • Dejan Savić Klinika za neurologiju, Univerzitetski Klinički Centar Niš, Niš, Republika Srbija
  • Nikola Krstić Medicinski fakultet Univerziteta u Nišu, Niš, Republika Srbija https://orcid.org/0000-0002-4398-1449
  • Ana Andrejević Medicinski fakultet Univerziteta u Nišu, Niš, Republika Srbija
  • Andrija Rančić Medicinski fakultet Univerziteta u Nišu, Niš, Republika Srbija https://orcid.org/0009-0007-6845-9458
  • Miljana Mladenović Medicinski fakultet Univerziteta u Nišu, Niš, Republika Srbija
  • Tatjana Jevtović-Stoimenov Medicinski fakultet Univerziteta u Nišu, Katedra Biohemija, Niš, Republika Srbija https://orcid.org/0000-0003-0600-5411
DOI: https://doi.org/10.5937/afmnai41-46218
Ključne reči: SNP, vitamin D receptor, vitamin D, neuroinflamatorne bolesti, multipla skleroza

Sažetak


Multipla skleroza (MS) je hronična, autoimuna, demijelinizaciona bolest centralnog nervnog Sistema. Dugo je poznata povezanost između deficita vitamina D, sunčeve svetlosti i visoke incidence multiple skleroze, a naknadne studije su potvrdile anti-inflamatorna i neuroprotektivna svojstva vitamina D. Vitamin D receptor (VDR) odgovoran je za većinu bioloških efekata vitamina D, a četri VDR polimorfizma indentifikovani su kao mogući faktori rizika za nastanak više autoimunih bolesti. Cilj našeg istraživanja bio je da se utvrdi da li u Srpskoj polulaciji postoji povezanost između nastanka multiple skleroze i učestalosti VDR polimofrgizama BsmI (rs7975232) I FokI (rs2228570). U našem istraživanju bilo je uključeno 169 ispitanika iz jugoistočne Srbije, od kojih je 80 imalo dijagnostifikovanu multiplu sklerozu. Za detekciju BsmI i FokI VDR polimorfizama korišen je PCR-RFLP metod. Postojala je statistički značajna razlika u distribuciji FokI genotipova I alela između pacijenata sa MS I kontrolne grupe (p= 0,006; p = 0,001). Nije bilo statistički značajne razlike između genotipova i alela BsmI polimorfizma između pacijenata sa multiplom sklerozom i zdravih ispitanika (p = 0,140; p = 0,153).

Biografije autora

Dejan Savić, Klinika za neurologiju, Univerzitetski Klinički Centar Niš, Niš, Republika Srbija

Docent

Nikola Krstić, Medicinski fakultet Univerziteta u Nišu, Niš, Republika Srbija

Istraživač saradnik

Tatjana Jevtović-Stoimenov, Medicinski fakultet Univerziteta u Nišu, Katedra Biohemija, Niš, Republika Srbija

Redovni profesor - Medicinski fakultet Univerziteta u Nišu, Katedra Biohemija

Reference

1.     Oh J, Vidal-Jordana A, Montalban X. Multiple sclerosis: clinical aspects. Curr Opin Neurol. 2018; 31(6):752-9.


2.     Savić D, Vojinović S, Lukić S, Savić Lj. Clinical and Neurophysiological Features in Patients Presenting Clinically Isolated Syndrome Suggestive on Multiple Sclerosis. Acta Facultatis Medicae Naissensis 2010; 27(2): 69-74.


3.     Acheson ED, Bachrach CA, Wright FM. Some comments on the relationship of the distribution of multiple sclerosis to latitude, solar radiation and other variables. Acta Psychiatr Scand Suppl 1960; 35(147):132-47.


4.     Pierrot-Deseilligny C, Souberbielle JC. Is hypovitaminosis D one of the enviromental risk factors for multiple sclerosis? Brain 2010;133(Pt 7):1869-88.


5.     Valdivielso JM, Fernandez E. Vitamin D receptor polymorphisms and diseases. Clin Chim Acta 2006; 371(1-2): 1-12.


6.     Wei R, Christakos S. Mechanisms underlying the regulation of innate and adaptive immunity by Vitamin D. Nutrients 2015; 7(10):8251-60.


7.     Provvedini DM, Tsoukas CD, Deftos LJ, Manolagas SC. 1,25-dihydroxyvitamin D3 receptors in human Leukocytes. Science 1983; 221(4616):1181-3.


8.     Peelen E, Knippenberg S, Muris AH, Thewissen M, Smolders J, Cohen Tervaert JW, et al. Effects of vitamin D on the peripheral adaptive immune system: A review. Autoimmun Rev 2011; 10(12):733-43.


9.     Moosavi E, Rafiei A, Yazdani Y, Eslami M, Saeedi M. Association of serum levels and receptor genes BsmI, TaqI and FokI polymorphisms of vitamin D with the severity of multiple sclerosis. J Clin Neurosci 2021; 84: 75-81.


10.  Bizzaro G, Antico A, Fortunato A, Bizzaro N. Vitamin D and Autoimmune Diseases: Is Vitamin D Receptor (VDR) Polymorphism the Culprit? Isr Med Assoc J 2017; 19(7):438-43.


11.  Xiaoying C, Gooch H, Petty A, McGrath JJ, Eyles D. Vitamin D and the brain: Genomic and non-genomic actions. Mol Cell Endocrinol 2017; 453: 131-43.


12.  Eyles DW, Almeras L, Benech P, Patatian A, Mackay-Sim A, McGrath J, et al. Developmental vitamin D deficiency alters the expression of genes encoding mitochondrial, cytoskeletal and synaptic proteins in the adult rat brain. J Steroid Biochem Mol Biol 2007; 103(3-5): 538-45.


13.  Bivona G, Gambinoa CM, Iacolinoa G, Ciaccio V. Vitamin D and the nervous system.  Neurol Res 2019; 41(9): 827-35.


14.  Stumpf WE, Sar M, Clark SA. Brain Target Sites for 1,25-Dihydroxyvitamin D3. Science 1982; 215(4538):1403-5.


15.  Eyles DW, Smith S, Kinobe R, Hewinson M, McGrath JJ. Distribution of the Vitamin D receptor and 1a-hydroxylase in human brain. J Chem Neuroanat 2005; 29(1): 21–30.


16.  Murua SR, Farez MF, Quintana FJ. The immune response in multiple sclerosis. Annu rev Pathol 2022; 17: 121-39.


17.  Bivona G, Agnello L, Ciaccio M. The immunological implication of the new vitamin D metabolism. Cent Eur J Immunol 2018; 43(3): 331-4.


18.  O’Gorman C, Lucas R, Taylor B. Environmental risk factors for multiple sclerosis: a review with a focus on molecular mechanisms. Int J Mol Sci 2012; 13: 11718-52.


19.  Soilu-Hanninen M, Airas L, Mononen I, Heikkila A, Viljanen M, Hanninen A. 25-hydroxyvitamin D levels in serum at he onset of multiple sclerosis. Mult Scler 2005; 11(3): 226-71.


20.  Smolders J, Menheere P, Kessels A, Damoiseaux J, Hupperts R. Association of vitamin D metabolite levels with relapse rate and disability in multiple sclerosis. Mult Scler 2008; 14(9): 1220-4.


21.  Niino M, Fukuzawa T, Kikuchi S, Sasaki H. Therapeutic potential of vitamin D for multiple sclerosis. Curr Med Chem 2008; 15(5): 499-505.


22.  Whitfield GK, Remus LS, Jurutka PW, Zitzer H, Oza AK, Dang HTL, et al. Functionally relevant polymorphisms in the human nuclear vitamin D receptor gene. Mol Cel Endocrinol 2001; 177(1): 145-56.


23.  van Etten E, Verlinden L, Giulietti A, Ramos-Lopez E, Branisteanu DD, Ferreira GB, et al. The vitamin D receptor gene FokI polymorphism: functional impact on the immune system. Eur J Immunol 2007; 37(2): 359-405.


24.  Gross C, Krishnan AV, Malloy PJ, Eccleshall TR, Zhao XY, Feldman D, et al. The vitamin D receptor gene start codon polymorphism: a functional analysis of FokI variants. J Bone Miner Res 1998; 13(11): 1691-9.


25.  Morrison NA, Qi JC, Tokita A, Kelly PJ, Crofts L, Nguyen TV, et al. Prediction of bone density from vitamin D receptor alleles. Nature 1994; 367: 284–7.


26.  Durrin LK, Haile RW, Ingles SA, Coetzee GA. Vitamin D receptor 3'-untranslated region polymorphisms: lack of effect on mRNA stability. Biochim Biophys Acta 1999; 1453(3):311-20.


27.  Agnello L, Scazzone C, Ragonese P, Salemi G, Lo Sasso B, Schillaci R, et al. Vitamin D receptor polymorphisms and 25-hydroxyvitamin D in a group of Sicilian multiple sclerosis patients. Neurol Sci 2016; 37(2): 261–7.


28.  Sioka C, Papakonstantinou S, Markoula S, Gkartziou F, Georgiou A, Georgiou I, et al. Vitamin D receptor gene polymorphisms in multiple sclerosis patients in northwest Greece. J Negat Results Biomed 2011; 10:3.


29.  Abdollahzadeh R, Fard MS, Rahmani F, Moloudi K, Kalani BS, Azarnezhad A. Predisposing role of vitamin D receptor (VDR) polymorphisms in the development of multiple sclerosis: a case-control study. J Neurol Sci 2016; 367: 148–51.


30.  Al-Temaimi RA, Al-Enezi A, Al-Serri A, Alroughani R, Al-Mulla F. The association of vitamin D receptor polymorphisms with multiple sclerosis in a case-control study from Kuwait. PLoS One 2015; 10(11): e0142265.


31.  Bermundez-Morales VH, Fierros G, Lopez RL, Martinez-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; 306: 20-4.


32.  Cierny D, Michalik J, Skerenova M, Kantorova E, Sivak Š, Javor J, et al. ApaI, BsmI and TaqI VDR gene polymorphisms in association with multiple sclerosis in Slovaks. Neurol Res 2016; 38(8): 678–84.


33.  Krenek P, Benesova Y, Bienertova-Vasku J, Vasku A. 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): 559-66.


34.  Kamisli O, Acar C, Sozen M, Tecellioglu M, Yücel FE, Vaizoglub D, et al. The Association between Vitamin D Receptor Polymorphisms and Multiple Sclerosis in a Turkish Population. Multi Scler Relat Disord 2018; 20: 78-81.


35.  Garcia-Martin E, Agundez JAG, Martinez C, Benito-Leon J, Millan-Pascual J, Calleja P, et al. Vitamin D3 receptor (VDR) gene rs2228570 (Fok1) and rs731236 (Taq1) variants are not associated with the risk for multiple sclerosis: results of a new study and a meta-analysis. PLOS ONE 2013; 8(6): e65487.


36.  Tizaoui K, Kaabachi W, Hamzaoui A, Hamzaoui K. Association between vitamin D receptor polymorphisms and multiple sclerosis: systematic review and meta-analysis of case-control studies. Cell Mol Immunol 2015; 12(2): 243-52.


37.  Zhang D, Wang L, Zhang R, Li S. Association of vitamin D receptor gene polymorphisms and risk of multiple sclerosis: a meta analysis. Arch Med Res 2019; 50(6): 350-61.


38.  Imani D, Razi B, Motallebnezhad M, Rezaei R. Association between vitamin D receptor (VDR) polymorphisms and the risk of multiple sclerosis (MS): an updated meta-analysis. BMC Neurol 2019; 19(1): 339.

Objavljeno
2025/11/19
Broj časopisa
Vol. 41 Br. 4 (2024): Acta facultatis medicae Naissensis
Rubrika
Originalni rad / Original article