The Association of Vitamin D Receptor Polymorphisms with Multiple Sclerosis in a Case-Control Study from Kuwait

Affiliations


Abstract

Vitamin D deficiency is associated with several diseases including multiple sclerosis (MS). Several factors influence vitamin D levels and its optimal multi-function maintenance. Our objective was to assess quantifiable variables influencing vitamin D level and metabolism in MS patients from Kuwait. In a case-control study involving 50 MS patients, and 50 healthy control individuals for which plasma vitamin D levels, supplement use, vitamin D receptor (VDR) variants, and skin pigmentation indices were ascertained; we found overall vitamin D levels to be deficient in both groups, and supplement use to be common practice. VDR variants TaqI and BsmI associated with MS risk, and ApaI associated with low disease progression. VDR variant FokI associated with higher vitamin D levels in both groups. We conclude that several quantifiable variables related to vitamin D associate with MS suggesting a possible clinical immuno-modulatory application of vitamin D for MS patients in Kuwait.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.


Similar articles

ApaI, BsmI and TaqI VDR gene polymorphisms in association with multiple sclerosis in Slovaks.

Čierny D, Michalik J, Škereňová M, Kantorová E, Sivák Š, Javor J, Kurča E, Dobrota D, Lehotský J.Neurol Res. 2016 Aug;38(8):678-84. doi: 10.1080/01616412.2016.1200287. Epub 2016 Jun 23.PMID: 27338176

Association of serum levels and receptor genes BsmI, TaqI and FokI polymorphisms of vitamin D with the severity of multiple sclerosis.

Moosavi E, Rafiei A, Yazdani Y, Eslami M, Saeedi M.J Clin Neurosci. 2021 Feb;84:75-81. doi: 10.1016/j.jocn.2020.12.008. Epub 2020 Dec 29.PMID: 33485603

Vitamin D receptor gene polymorphisms are associated with multiple sclerosis in Mexican adults.

Bermúdez-Morales VH, Fierros G, Lopez RL, Martínez-Nava G, Flores-Aldana M, Flores-Rivera J, Hernández-Girón C.J Neuroimmunol. 2017 May 15;306:20-24. doi: 10.1016/j.jneuroim.2017.01.009. Epub 2017 Feb 3.PMID: 28385183

Vitamin D-gene interactions in multiple sclerosis.

Berlanga-Taylor AJ, Disanto G, Ebers GC, Ramagopalan SV.J Neurol Sci. 2011 Dec 15;311(1-2):32-6. doi: 10.1016/j.jns.2011.08.041. Epub 2011 Oct 13.PMID: 22000399 Review.

Multiple sclerosis, osteoporosis, and vitamin D.

Sioka C, Kyritsis AP, Fotopoulos A.J Neurol Sci. 2009 Dec 15;287(1-2):1-6. doi: 10.1016/j.jns.2009.09.012. Epub 2009 Oct 2.PMID: 19800081 Review.


Cited by

Distribution of vitamin D-binding protein/group-specific component gene subtypes in Kuwaiti population.

Al-Shammri SN, Mustafa AS, Bhattacharya A.Mol Genet Genomic Med. 2022 May;10(5):e1930. doi: 10.1002/mgg3.1930. Epub 2022 Mar 29.PMID: 35349224 Free PMC article.

Vitamin D and Genetic Susceptibility to Multiple Sclerosis.

Scazzone C, Agnello L, Bivona G, Lo Sasso B, Ciaccio M.Biochem Genet. 2021 Feb;59(1):1-30. doi: 10.1007/s10528-020-10010-1. Epub 2020 Nov 7.PMID: 33159645 Review.

Replication analysis of variants associated with multiple sclerosis risk.

Dashti M, Ateyah K, Alroughani R, Al-Temaimi R.Sci Rep. 2020 Apr 30;10(1):7327. doi: 10.1038/s41598-020-64432-3.PMID: 32355262 Free PMC article.

Vitamin D and Disease Severity in Multiple Sclerosis-Baseline Data From the Randomized Controlled Trial (EVIDIMS).

Bäcker-Koduah P, Bellmann-Strobl J, Scheel M, Wuerfel J, Wernecke KD, Dörr J, Brandt AU, Paul F.Front Neurol. 2020 Feb 25;11:129. doi: 10.3389/fneur.2020.00129. eCollection 2020.PMID: 32158426 Free PMC article.

Association between vitamin D receptor (VDR) polymorphisms and the risk of multiple sclerosis (MS): an updated meta-analysis.

Imani D, Razi B, Motallebnezhad M, Rezaei R.BMC Neurol. 2019 Dec 26;19(1):339. doi: 10.1186/s12883-019-1577-y.PMID: 31878897 Free PMC article.


KMEL References


References

  1.  
    1. Autier P, Boniol M, Pizot C, Mullie P. Vitamin D status and ill health: a systematic review. Lancet Diabetes Endocrinol. 2014. January;2(1):76–89. Epub 2014/03/14. eng. 10.1016/S2213-8587(13)70165-7 - DOI - PubMed
  2.  
    1. Munger KL, Kochert K, Simon KC, Kappos L, Polman CH, Freedman MS, et al. Molecular mechanism underlying the impact of vitamin D on disease activity of MS. Ann Clin Transl Neurol. 2014. August;1(8):605–17. Pubmed Central PMCID: 4180413. Epub 2014/10/07. eng. 10.1002/acn3.91 - DOI - PMC - PubMed
  3.  
    1. Ascherio A, Munger KL, White R, Kochert K, Simon KC, Polman CH, et al. Vitamin D as an early predictor of multiple sclerosis activity and progression. JAMA Neurol. 2014. March;71(3):306–14. Pubmed Central PMCID: 4000029. Epub 2014/01/22. eng. 10.1001/jamaneurol.2013.5993 - DOI - PMC - PubMed
  4.  
    1. Martinelli V, Dalla Costa G, Colombo B, Dalla Libera D, Rubinacci A, Filippi M, et al. Vitamin D levels and risk of multiple sclerosis in patients with clinically isolated syndromes. Mult Scler. 2014. February;20(2):147–55. Epub 2013/07/10. eng. 10.1177/1352458513494959 - DOI - PubMed
  5.  
    1. Antico A, Tampoia M, Tozzoli R, Bizzaro N. Can supplementation with vitamin D reduce the risk or modify the course of autoimmune diseases? A systematic review of the literature. Autoimmun Rev. 2012. December;12(2):127–36. Epub 2012/07/11. eng. 10.1016/j.autrev.2012.07.007 - DOI - PubMed
  6.  
    1. VanAmerongen BM, Dijkstra CD, Lips P, Polman CH. Multiple sclerosis and vitamin D: an update. Eur J Clin Nutr. 2004. August;58(8):1095–109. . Epub 2004/04/01. eng. - PubMed
  7.  
    1. al-Din AS, Khogali M, Poser CM, al-Nassar KE, Shakir R, Hussain J, et al. Epidemiology of multiple sclerosis in Arabs in Kuwait: a comparative study between Kuwaitis and Palestinians. Journal of the neurological sciences. 1990. December;100(1–2):137–41. . - PubMed
  8.  
    1. Alroughani R, Ahmed SF, Behbahani R, Khan R, Thussu A, Alexander KJ, et al. Increasing prevalence and incidence rates of multiple sclerosis in Kuwait. Multiple sclerosis. 2014. April;20(5):543–7. 10.1177/1352458513504328 - DOI - PubMed
  9.  
    1. Fields J, Trivedi NJ, Horton E, Mechanick JI. Vitamin D in the Persian Gulf: integrative physiology and socioeconomic factors. Curr Osteoporos Rep. 2011. December;9(4):243–50. Epub 2011/09/09. eng. 10.1007/s11914-011-0071-2 - DOI - PubMed
  10.  
    1. Webb AR. Who, what, where and when-influences on cutaneous vitamin D synthesis. Prog Biophys Mol Biol. 2006. September;92(1):17–25. . Epub 2006/06/13. eng. - PubMed
  11.  
    1. Stocklin E, Eggersdorfer M. Vitamin D, an essential nutrient with versatile functions in nearly all organs. Int J Vitam Nutr Res. 2013;83(2):92–100. Epub 2014/02/05. eng. 10.1024/0300-9831/a000151 - DOI - PubMed
  12.  
    1. Harms LR, Burne TH, Eyles DW, McGrath JJ. Vitamin D and the brain. Best Pract Res Clin Endocrinol Metab. 2011. August;25(4):657–69. Epub 2011/08/30. eng. 10.1016/j.beem.2011.05.009 - DOI - PubMed
  13.  
    1. Lang PO, Aspinall R. Can we translate vitamin D immunomodulating effect on innate and adaptive immunity to vaccine response? Nutrients. 2015. March;7(3):2044–60. Pubmed Central PMCID: 4377899. Epub 2015/03/25. eng. 10.3390/nu7032044 - DOI - PMC - PubMed
  14.  
    1. Fernandes de Abreu DA, Eyles D, Feron F. Vitamin D, a neuro-immunomodulator: implications for neurodegenerative and autoimmune diseases. Psychoneuroendocrinology. 2009. December;34 Suppl 1:S265–77. Epub 2009/06/24. eng. 10.1016/j.psyneuen.2009.05.023 - DOI - PubMed
  15.  
    1. Uitterlinden AG, Fang Y, van Meurs JB, van Leeuwen H, Pols HA. Vitamin D receptor gene polymorphisms in relation to Vitamin D related disease states. J Steroid Biochem Mol Biol. 2004. May;89-90(1–5):187–93. . Epub 2004/07/01. eng. - PubMed
  16.  
    1. Huang J, Xie ZF. Polymorphisms in the vitamin D receptor gene and multiple sclerosis risk: a meta-analysis of case-control studies. J Neurol Sci. 2012. February 15;313(1–2):79–85. Epub 2011/10/28. eng. 10.1016/j.jns.2011.09.024 - DOI - PubMed
  17.  
    1. 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. March;12(2):243–52. Epub 2014/07/08. eng. 10.1038/cmi.2014.47 - DOI - PMC - PubMed
  18.  
    1. Laaser U, Senault R, Viefhues H, Deutsche Gesellschaft für Sozialmedizin., Deutsches Institut zur Bekämpfung des Hohen Blutdruckes. Primary health care in the making Berlin; New York: Springer-Verlag; 1985. xxiv, 545 p. p.
  19.  
    1. Al-Temaimi R, Alroughani R, Jacob S, Al-Mulla F. Gender influence in EBV antibody response in multiple sclerosis patients from Kuwait. Journal of neuroimmunology. 2015. August 15;285:57–61. 10.1016/j.jneuroim.2015.05.021 - DOI - PubMed
  20.  
    1. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. The Journal of clinical endocrinology and metabolism. 2011. July;96(7):1911–30. 10.1210/jc.2011-0385 - DOI - PubMed
  21.  
    1. Nessvi S, Johansson L, Jopson J, Stewart A, Reeder A, McKenzie R, et al. Association of 25-hydroxyvitamin D3)levels in adult New Zealanders with ethnicity, skin color and self-reported skin sensitivity to sun exposure. Photochem Photobiol. 2011. Sep-Oct;87(5):1173–8. Epub 2011/06/18. eng. 10.1111/j.1751-1097.2011.00956.x - DOI - PubMed
  22.  
    1. 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. March 30;1453(3):311–20. . Epub 1999/04/02. eng. - PubMed
  23.  
    1. Narooie-Nejad M, Moossavi M, Torkamanzehi A, Moghtaderi A, Salimi S. Vitamin D Receptor Gene Polymorphism and the Risk of Multiple Sclerosis in South Eastern of Iran. J Mol Neurosci. 2015. February 18 . Epub 2015/04/10. Eng. - PubMed
  24.  
    1. Narooie-Nejad M, Moossavi M, Torkamanzehi A, Moghtaderi A. Positive association of vitamin D receptor gene variations with multiple sclerosis in South East Iranian population. Biomed Res Int. 2015;2015:427519 Pubmed Central PMCID: 4320885. Epub 2015/02/17. eng. 10.1155/2015/427519 - DOI - PMC - PubMed
  25.  
    1. Ben-Selma W, Ben-Fredj N, Chebel S, Frih-Ayed M, Aouni M, Boukadida J. Age- and gender-specific effects on VDR gene polymorphisms and risk of the development of multiple sclerosis in Tunisians: a preliminary study. Int J Immunogenet. 2015. April 20. - PubMed
  26.  
    1. Tajouri L, Ovcaric M, Curtain R, Johnson MP, Griffiths LR, Csurhes P, et al. Variation in the vitamin D receptor gene is associated with multiple sclerosis in an Australian population. J Neurogenet. 2005. Jan-Mar;19(1):25–38. . Epub 2005/08/04. eng. - PubMed
  27.  
    1. Fukazawa T, Yabe I, Kikuchi S, Sasaki H, Hamada T, Miyasaka K, et al. Association of vitamin D receptor gene polymorphism with multiple sclerosis in Japanese. J Neurol Sci. 1999. June 15;166(1):47–52. . Epub 1999/08/28. eng. - PubMed
  28.  
    1. Dickinson JL, Perera DI, van der Mei AF, Ponsonby AL, Polanowski AM, Thomson RJ, et al. Past environmental sun exposure and risk of multiple sclerosis: a role for the Cdx-2 Vitamin D receptor variant in this interaction. Mult Scler. 2009. May;15(5):563–70. Epub 2009/04/23. eng. 10.1177/1352458509102459 - DOI - PubMed
  29.  
    1. Smolders J, Damoiseaux J, Menheere P, Tervaert JW, Hupperts R. Association study on two vitamin D receptor gene polymorphisms and vitamin D metabolites in multiple sclerosis. Ann N Y Acad Sci. 2009. September;1173:515–20. Epub 2009/09/18. eng. 10.1111/j.1749-6632.2009.04656.x - DOI - PubMed
  30.  
    1. 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 Pubmed Central PMCID: 3097159. Epub 2011/05/07. eng. 10.1186/1477-5751-10-3 - DOI - PMC - PubMed
  31.  
    1. Garcia-Martin E, Agundez JA, 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 Pubmed Central PMCID: 3688728. Epub 2013/07/11. eng. 10.1371/journal.pone.0065487 - DOI - PMC - PubMed
  32.  
    1. Agliardi C, Guerini FR, Saresella M, Caputo D, Leone MA, Zanzottera M, et al. Vitamin D receptor (VDR) gene SNPs influence VDR expression and modulate protection from multiple sclerosis in HLA-DRB1*15-positive individuals. Brain Behav Immun. 2011. October;25(7):1460–7. Epub 2011/06/15. eng. 10.1016/j.bbi.2011.05.015 - DOI - PubMed
  33.  
    1. Uitterlinden AG, Fang Y, Van Meurs JB, Pols HA, Van Leeuwen JP. Genetics and biology of vitamin D receptor polymorphisms. Gene. 2004. September 1;338(2):143–56. . Epub 2004/08/19. eng. - PubMed
  34.  
    1. Christensen MH, Apalset EM, Nordbo Y, Varhaug JE, Mellgren G, Lien EA. 1,25-dihydroxyvitamin D and the vitamin D receptor gene polymorphism Apa1 influence bone mineral density in primary hyperparathyroidism. PLoS One. 2013;8(2):e56019 Pubmed Central PMCID: 3572149. Epub 2013/02/19. eng. 10.1371/journal.pone.0056019 - DOI - PMC - PubMed
  35.  
    1. V ON, Asani FF, Jeffery TJ, Saccone DS, Bornman L. Vitamin D Receptor Gene Expression and Function in a South African Population: Ethnicity, Vitamin D and I. PLoS One. 2013;8(6):e67663 . Pubmed Central PMCID: 3689684. Epub 2013/06/28. Eng. - PMC - PubMed
  36.  
    1. Whitfield GK, Remus LS, Jurutka PW, Zitzer H, Oza AK, Dang HT, et al. Functionally relevant polymorphisms in the human nuclear vitamin D receptor gene. Mol Cell Endocrinol. 2001. May 25;177(1–2):145–59. . Epub 2001/05/30. eng. - PubMed
  37.  
    1. Alimirah F, Peng X, Murillo G, Mehta RG. Functional significance of vitamin D receptor FokI polymorphism in human breast cancer cells. PLoS One. 2011;6(1):e16024 Pubmed Central PMCID: 3025916. Epub 2011/02/02. eng. 10.1371/journal.pone.0016024 - DOI - PMC - PubMed
  38.  
    1. Hagenau T, Vest R, Gissel TN, Poulsen CS, Erlandsen M, Mosekilde L, et al. Global vitamin D levels in relation to age, gender, skin pigmentation and latitude: an ecologic meta-regression analysis. Osteoporos Int. 2009. January;20(1):133–40. Epub 2008/05/07. eng. 10.1007/s00198-008-0626-y - DOI - PubMed
  39.  
    1. Smolders J, Damoiseaux J, Menheere P, Tervaert JW, Hupperts R. Fok-I vitamin D receptor gene polymorphism (rs10735810) and vitamin D metabolism in multiple sclerosis. J Neuroimmunol. 2009. February 15;207(1–2):117–21. Epub 2009/01/31. eng. 10.1016/j.jneuroim.2008.12.011 - DOI - PubMed