Predisposing role of vitamin D receptor (VDR) polymorphisms in the development of multiple sclerosis: A case-control study

Abdollahzadeh, Rasoul; Fard, Mahsa Sobhani; Rahmani, Farideh; Moloudi, Kaveh; Kalani, Behrooz Sadeghi; Azarnezhad, Asaad

doi:10.1016/j.jns.2016.05.053

Cited by 35 publications

(33 citation statements)

References 34 publications

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“…Our results are consistent with some studies reported in the literature for various populations. A study in Iran reported that there was a significant difference in genotype distribution between case and control groups for polymorphism and allelic frequency for ApaI, BsmI and TaqI (15). A Japanese group found a higher frequency of the ApaI AA genotype and A allele in MS (16).…”

Section: Resultsmentioning

confidence: 99%

Vitamin D receptor gene polymorphisms in multiple sclerosis disease: A case-control study

Çakına

Ocak

Özkan

et al. 2018

Revista Romana De Medicina De Laborator

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Multiple sclerosis (MS) is a common neurologic disorder that is a chronic inflammatory, demyelinating, and neurodegenerative disease of the central nervous system (CNS). Its etiology remains unknown. Several recent studies have found that decreased susceptibility to vitamin D deficiency is also associated with a decreased risk of MS. The role of vitamin D receptor (VDR) gene and its polymorphisms are highlighted as susceptible components. In this study, we aimed to identify the relationship between ApaI (rs7975232), BsmI (rs 1544410), and TaqI (rs731236) gene polymorphisms with MS. ApaI, BsmI, and TaqI genotypes were determined in 70 patients with MS and in 70 control subjects. DNA was isolated from blood samples, and then ApaI, BsmI and TaqI gene polymorphisms were identified using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The distribution of BsmI and TaqI polymorphisms did not show any significant differences in MS patients and controls; however, increased A allele of ApaI polymorphism was found in MS patients. Our findings suggest that the ApaI gene polymorphism might be associated with MS. Investigation of a larger population and functional work on these gene structures and function in MS patients are recommended.

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Section: Resultsmentioning

confidence: 99%

Vitamin D receptor gene polymorphisms in multiple sclerosis disease: A case-control study

Çakına

Ocak

Özkan

et al. 2018

Revista Romana De Medicina De Laborator

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“…A case-controlled study including 160 patients with MS and 150 healthy controls revealed the protective role of TT genotype of Taq I (ORs| < |1), CC genotype of Apal , and GG genotype of Bsm I (ORs| < |1), suggesting that VDR polymorphisms seem to have a notable connection with MS pathogenesis; however, studies in big population that analyze the functional work on the gene structure and its function are needed (109). Another study in 158 European Caucasians with ulcerative colitis, 245 with Crohn’s disease and 164 cadaveric renal allograft donor controls demonstrated that there were significantly more people who were homozygous for the Taq I polymorphism at codon 352 of exon 8 (genotype tt) among patients with Crohn’s disease (frequency 0.22) than patients with ulcerative colitis (0.12) or controls (0.12) (110).…”

Section: Discussionmentioning

confidence: 99%

Role of Vitamin D in the Hygiene Hypothesis: The Interplay between Vitamin D, Vitamin D Receptors, Gut Microbiota, and Immune Response

2016

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The hygiene hypothesis postulates that higher levels of cleanliness and improper exposure to microorganisms early in childhood could disturb the intestinal microbiome resulting in abnormal immune responses. Recently, more attention has been put on how a lack of sun exposure and consequently vitamin D deficiency could lead to less immune tolerance and aberrant immune responses. Moreover, vitamin D receptor (VDR) function has been positioned to be a critical aspect of immune response and gut homeostasis. Therefore, this review focuses on the role that the interaction between vitamin D, VDR function, and gut microbiome might have on autoimmune diseases in the context of the hygiene hypothesis. Literature shows that there is a high correlation between vitamin D deficiency, VDR dysfunction, gut microbiota composition, and autoimmune diseases. The biologically active form of vitamin D, 1,25(OH)2D3, serves as the primary ligand for VDRs, which have been shown to play a fundamental role in reducing autoimmune disease symptoms. Although the biological functions of VDR, the effects of its genetic variants, and the effects of epigenetic profiles in its promoter region are largely unknown in humans, studies in murine models are increasingly demonstrating that VDRs play a crucial role in attenuating autoimmune disease symptoms by regulating autophagy and the production of antimicrobial peptides, such cathelicidin and β-defensin, which are responsible for modifying the intestinal microbiota to a healthier composition. Remarkably, evidence shows that hormonal compounds and byproducts of the microbiota such as secondary bile acids might also activate VDR. Therefore, understanding the interaction between VDR and gut microbiota is of the utmost importance toward understanding the rise in autoimmune diseases in Western countries. We have gained insights on how the VDR functions affects inflammation, autophagy, and microbiota composition that could lead to the development of pathogenesis of autoimmune diseases, while confirming the role vitamin D and VDRs have in the context of hygiene hypothesis.

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“…In the perspective of substantial results from experimental work, reliable epidemiological information, and encouraging clinical findings, the theory that hypovitaminosis D as one of MS risk factors has quickly gained support and can, before long, be affirmed by more broad clinical studies. Vitamin D (VD) role in MS pathogenesis was highlighted in several studies that showed decreased level of active form of VD in initial and serious phases of MS [5][6][7][8]. Genetic variations in vitamin D receptor (VDR) gene as single nucleotide polymorphisms (SNPs) might alter VD-VDR pathway causing disturbance of VD immune-regulatory functions which consequently is reflected on MS risk [9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

“…Presence of FokI restriction enzyme site results in the variant "f" allele and translation of a 3 amino acid longer VDR protein, while the "F" allele, the wild type, produces shorter VDR protein and is associated with an increased transcriptional activity [13]. Other VDR SNPs are located in the 3′UTR and defined by the restriction enzymes as BsmI polymorphism (rs1544410) A/G in intron 8, ApaI polymorphism (rs7975232) G/T in intron 8, TaqI polymorphism (rs731236) T/C in exon 9, and Tru9I polymorphism (rs757343) G/A in intron 8 [6][7][8][14][15][16][17][18]. Considering each SNP site independently may not uncover critical impacts or clarify variations of numerous endeavors to associate VDR genotype with MS [7,[19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Protective association of VDR gene polymorphisms and haplotypes with multiple sclerosis patients in Egyptian population

Hassab

Deif

Elneely

et al. 2019

Egypt J Med Hum Genet

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Background: Hypovitaminosis D is one of the hazardous factors for multiple sclerosis (MS) and can be attested by expanding clinical studies. We aimed to study vitamin D receptor (VDR) gene polymorphisms: FokI, BsmI, ApaI, TaqI, and Tru9I genotype; frequency; haplotype structure; and linkage disequilibrium (LD) in MS Egyptian patients. The study was conducted on 50 MS patients and 50 healthy controls of matching age and sex. Alleles and genotype variants of VDR gene SNPs were analyzed by PCR using the restriction fragment length polymorphism (RFLP). Haplotype and linkage disequilibrium analysis based on the five genetic loci was studied on the detected genotypes. Results: Frequency of FokI genotype (Ff+ff) was significantly higher in healthy controls (50%) compared to MS (28%) (P = 0.03), and "f" allele was significantly associated with the control group (OR = 0.42, CI = 0.26-0.85, P = 0.015). Frequency of ApaI genotype (Aa+aa) was significantly higher in MS (60%) (P = 0.002), and "a" allele was significantly associated with MS cases (OR = 2.47, CI = 1.25-4.88, P = 0.008). TaqI allelic distribution showed significant association of "t" allele with control group (OR = 0.55, CI = 0.31-0.98, P = 0.04). Statistically significant LD was detected between BsmI and ApaI in controls and MS (D' = 0.89 and P < 0.001, and D' = 0.52 and P < 0.001), respectively. Odd ratios of "fAt" and "BAt" were 0.2 (95% CI = 0.06-0.66) and 0.43 (95% CI = 0.19-0.97), respectively, suggesting that MS risk was 5 times and 2.3 times lesser, respectively, for haplotype carriers compared to non-carriers. Conclusion: The study findings suggest that VDR gene variants "f," "A," and "t" alleles as well as VDR gene haplotypes "BAt" and "fAt" may have a protective effect against MS disease in Egyptian population.

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Predisposing role of vitamin D receptor (VDR) polymorphisms in the development of multiple sclerosis: A case-control study

Cited by 35 publications

References 34 publications

Vitamin D receptor gene polymorphisms in multiple sclerosis disease: A case-control study

Vitamin D receptor gene polymorphisms in multiple sclerosis disease: A case-control study

Role of Vitamin D in the Hygiene Hypothesis: The Interplay between Vitamin D, Vitamin D Receptors, Gut Microbiota, and Immune Response

Protective association of VDR gene polymorphisms and haplotypes with multiple sclerosis patients in Egyptian population

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