The Impact of Genetic Variants Related to Vitamin D and Autoimmunity: A Systematic Review

Overview

Journal Heliyon

Specialty Social Sciences

Date 2024 May 1

PMID 38689997

Authors

Luisa Menezes Trefilio

Leticia Bottino

Rafaella de Carvalho Cardoso

Guilherme Carneiro Montes

Fabricia Lima Fontes-Dantas

Affiliations

Soon will be listed here.

Abstract

Over the past few years, there has been a notable increment in scientific literature aimed at unraveling the genetic foundations of vitamin D signaling and its implications for susceptibility to autoimmunity, however, most of them address isolated diseases. Here, we conducted a systematic review of genetic variants related to vitamin D and autoimmune diseases and we discussed the current landscape of susceptibility and outcomes. Of 65 studies analyzed, most variants cited are in vitamin D binding protein (; rs2282679 GC gene), 25-hydroxylase (rs10751657 ), 1α-hydroxylase (rs10877012, ) and the nuclear hormone receptor superfamily [I (rs2228570), I (rs1544410), I (rs7975232), and I (rs731236) in gene]. Therefore, our findings confirmed the associations of several genetic variants of vitamin D signaling with a broad spectrum of autoimmune diseases/traits. In addition, given the low number of papers found with functional analysis, further studies to elucidate the real effect that the variants exert on Vitamin D signaling are recommended.

Citing Articles

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References

Hardin J . Dendritic cells: potential triggers of autoimmunity and targets for therapy. Ann Rheum Dis. 2005; 64 Suppl 4:iv86-90. PMC: 1766899. DOI: 10.1136/ard.2005.044560. View

Brink M, Johansson L, Nygren E, Arlestig L, Hultdin J, Rantapaa-Dahlqvist S . Vitamin D in individuals before onset of rheumatoid arthritis - relation to vitamin D binding protein and its associated genetic variants. BMC Rheumatol. 2019; 2:26. PMC: 6390591. DOI: 10.1186/s41927-018-0033-8. View

Hayes D . Vitamin D and ageing. Biogerontology. 2009; 11(1):1-16. DOI: 10.1007/s10522-009-9252-0. View

Zhuang J, Huang Z, Zhao G, Yu H, Li Z, Wu Z . Variants of CYP27B1 are associated with both multiple sclerosis and neuromyelitis optica patients in Han Chinese population. Gene. 2014; 557(2):236-9. DOI: 10.1016/j.gene.2014.12.045. View

Luo X, Yang M, Wu F, Wu L, Chen L, Tang Z . Vitamin D receptor gene BsmI polymorphism B allele, but not BB genotype, is associated with systemic lupus erythematosus in a Han Chinese population. Lupus. 2011; 21(1):53-9. DOI: 10.1177/0961203311422709. View

Karohl C, Su S, Kumari M, Tangpricha V, Veledar E, Vaccarino V . Heritability and seasonal variability of vitamin D concentrations in male twins. Am J Clin Nutr. 2010; 92(6):1393-8. PMC: 2980965. DOI: 10.3945/ajcn.2010.30176. View

Pani M, Regulla K, Segni M, Hofmann S, Hufner M, Pasquino A . A polymorphism within the vitamin D-binding protein gene is associated with Graves' disease but not with Hashimoto's thyroiditis. J Clin Endocrinol Metab. 2002; 87(6):2564-7. DOI: 10.1210/jcem.87.6.8562. View

Panierakis C, Goulielmos G, Mamoulakis D, Petraki E, Papavasiliou E, Galanakis E . Vitamin D receptor gene polymorphisms and susceptibility to type 1 diabetes in Crete, Greece. Clin Immunol. 2009; 133(2):276-81. DOI: 10.1016/j.clim.2009.08.004. View

Beaumont K, Newton R, Smit D, Leonard J, Stow J, Sturm R . Altered cell surface expression of human MC1R variant receptor alleles associated with red hair and skin cancer risk. Hum Mol Genet. 2005; 14(15):2145-54. DOI: 10.1093/hmg/ddi219. View

10.

van der Slik A, van den Eng I, Eerligh P, Doxiadis I, Koeleman B, Roep B . Sequence variation within the major histocompatibility complex subregion centromeric of HLA class II in type 1 diabetes. Tissue Antigens. 2007; 69(4):348-53. DOI: 10.1111/j.1399-0039.2007.00820.x. View

11.

Uitterlinden A, Fang Y, van Meurs J, Pols H, van Leeuwen J . Genetics and biology of vitamin D receptor polymorphisms. Gene. 2004; 338(2):143-56. DOI: 10.1016/j.gene.2004.05.014. View

12.

Triantos C, Aggeletopoulou I, Mantzaris G, Mouzaki A . Molecular basis of vitamin D action in inflammatory bowel disease. Autoimmun Rev. 2022; 21(8):103136. DOI: 10.1016/j.autrev.2022.103136. View

13.

Sonnenberg A, McCarty D, Jacobsen S . Geographic variation of inflammatory bowel disease within the United States. Gastroenterology. 1991; 100(1):143-9. DOI: 10.1016/0016-5085(91)90594-b. View

14.

Bailey R, Cooper J, Zeitels L, Smyth D, Yang J, Walker N . Association of the vitamin D metabolism gene CYP27B1 with type 1 diabetes. Diabetes. 2007; 56(10):2616-21. PMC: 2493063. DOI: 10.2337/db07-0652. View

15.

Laplana M, Sanchez-de-la-Torre M, Puig T, Caruz A, Fibla J . Vitamin-D pathway genes and HIV-1 disease progression in injection drug users. Gene. 2014; 545(1):163-9. DOI: 10.1016/j.gene.2014.04.035. View

16.

Doody K, Bourdeau A, Tremblay M . T-cell protein tyrosine phosphatase is a key regulator in immune cell signaling: lessons from the knockout mouse model and implications in human disease. Immunol Rev. 2009; 228(1):325-41. DOI: 10.1111/j.1600-065X.2008.00743.x. View

17.

Maalej A, Petit-Teixeira E, Michou L, Rebai A, Cornelis F, Ayadi H . Association study of VDR gene with rheumatoid arthritis in the French population. Genes Immun. 2005; 6(8):707-11. DOI: 10.1038/sj.gene.6364260. View

18.

Braun A, BICHLMAIER R, CLEVE H . Molecular analysis of the gene for the human vitamin-D-binding protein (group-specific component): allelic differences of the common genetic GC types. Hum Genet. 1992; 89(4):401-6. DOI: 10.1007/BF00194311. View

19.

Hering L, Katkeviciute E, Schwarzfischer M, Busenhart P, Gottier C, Mrdjen D . Protein Tyrosine Phosphatase Non-Receptor Type 2 Function in Dendritic Cells Is Crucial to Maintain Tissue Tolerance. Front Immunol. 2020; 11:1856. PMC: 7462014. DOI: 10.3389/fimmu.2020.01856. View

20.

Olliver M, Spelmink L, Hiew J, Meyer-Hoffert U, Henriques-Normark B, Bergman P . Immunomodulatory effects of vitamin D on innate and adaptive immune responses to Streptococcus pneumoniae. J Infect Dis. 2013; 208(9):1474-81. DOI: 10.1093/infdis/jit355. View