Vitamin D receptor genetic polymorphisms and the risk of multiple sclerosis: A systematic review and meta-analysis

Mohammadi, Asghar; Azarnezhad, Asaad; Khanbabaei, Hashem; Izadpanah, Esmael; Abdollahzadeh, Rasoul; Barreto, George E.; Sahebkar, Amirhossein

doi:10.1016/j.steroids.2020.108615

Cited by 24 publications

(20 citation statements)

References 33 publications

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“…This could be explained by the involvement of several factors determining the severity of the disease and might not be directly related to ApaI effects. Association of ApaI with different conditions including cancers, type 1 diabetes, asthma, multiple sclerosis, and several autoimmune diseases has previously been reported ( Clendenen et al, 2008 ; Cheon et al, 2015 ; Mohammadi et al, 2020 ; Wjst, 2005 ).…”

Section: Discussionmentioning

confidence: 88%

“…The expression and regulation of VDR itself are influenced by several mechanisms, including cell-type-specific transcription factors (TFs), auto-regulation by vitamin D, methylation of its primary promoter, and genetic variations ( Saccone et al, 2015 ). Genetic variations in the VDR gene such as SNPs might alter the function VD/VDR pathway in bronchial epithelium and immune-regulatory functions, which consequently influence the susceptibility to a large number of diverse conditions ( Valdivielso and Fernandez, 2006 ; Laplana et al, 2018 ; Mohammadi et al, 2020 ; Mehrabani et al, 2019 ) and possibly COVID-19.…”

Section: Discussionmentioning

confidence: 99%

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Association of Vitamin D receptor gene polymorphisms and clinical/severe outcomes of COVID-19 patients

Abdollahzadeh

Shushizadeh

Barazandehrokh

et al. 2021

Infection, Genetics and Evolution

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Introduction Growing evidence documented the critical impacts of vitamin D (VD) in the prognosis of COVID-19 patients. The functions of VD are dependent on the vitamin D receptor (VDR) in the VD/VDR signaling pathway. Therefore, we aimed to assess the association of VDR gene polymorphisms with COVID-19 outcomes. Methods In the present study, eight VDR single nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 500 COVID-19 patients in Iran, including 160 asymptomatic, 250 mild/moderate, and 90 severe/critical cases. The association of these polymorphisms with severity, clinical outcomes, and comorbidities were evaluated through the calculation of the Odds ratio (OR). Results Interestingly, significant associations were disclosed for some of the SNP-related alleles and/or genotypes in one or more genetic models with different clinical data in COVID-19 patients. Significant association of VDR-SNPs with signs, symptoms, and comorbidities was as follows: Apa I with shortness of breath (P ˂ 0.001) and asthma (P = 0.034) in severe/critical patients (group III); Bsm I with chronic renal disease (P = 0.010) in mild/moderate patients (group II); Tru9I with vomiting (P = 0.031), shortness of breath (P = 0.04), and hypertension (P = 0.030); Fok I with fever and hypertension (P = 0.027) in severe/critical patients (group III); CDX2 with shortness of breath (P = 0.022), hypertension (P = 0.036), and diabetes (P = 0.042) in severe/critical patients (group III); Eco RV with diabetes (P ˂ 0.001 and P = 0.045 in mild/moderate patients (group II) and severe/critical patients (group III), respectively). However, the association of VDR TaqI and Bgl I polymorphisms with clinical symptoms and comorbidities in COVID-19 patients was not significant. Conclusion VDR gene polymorphisms might play critical roles in the vulnerability to infection and severity of COVID-19, probably by altering the risk of comorbidities. However, these results require further validation in larger studies with different ethnicities and geographical regions.

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Association of Vitamin D receptor gene polymorphisms and clinical/severe outcomes of COVID-19 patients

Abdollahzadeh

Shushizadeh

Barazandehrokh

et al. 2021

Infection, Genetics and Evolution

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“…Growing evidence suggests that vitamin D is an environmental factor significantly affecting MS prevalence that is closely associated with the latitudinal gradient, where an increased exposure to UVB stimulates the cutaneous production of vitamin D reducing the risk of disease [71,72]. Accordingly, low levels of 25(OH)D, in association with the presence of genetic polymorphisms involving the metabolism of vitamin D, imply a greater risk of developing MS [73][74][75]. In addition, it has been observed that the presence of gene variants of the CYP27B1 seems to increase the risk and activity of MS [76][77][78].…”

Section: Multiple Sclerosismentioning

confidence: 99%

The role of vitamin D in autoimmune diseases: could sex make the difference?

et al. 2021

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Over the last decades, a central role for vitamin D in immune modulation has been well established. The active form of vitamin D, i.e., 1,25-dihydroxyvitamin D, through the interaction with vitamin D receptor, exerts different activities on the innate and adaptive immune system, among which suppression of inflammation and promotion of tolerogenic responses. Vitamin D insufficiency has been linked to autoimmune disorders that commonly display significant differences between females and males due to genetic, epigenetic, hormonal, and environmental factors. Notably, a number of studies recently showed a cross-talk between vitamin D and the sex hormone estrogen. Estrogen-mediated effects on immune response may favor a Th1 profile or a Th2 profile, depending on hormone concentration. Thus, estrogen-mediated effects appear to be variable on autoimmunity depending on its concentration but also on the pathogenic mechanisms underlying the different autoimmune diseases (i.e., Th1- or Th2-mediated diseases). Notably, estrogen has been demonstrated to enhance vitamin D function favoring its accumulation, and increasing the expression of vitamin D receptor, thus resulting in a more potent anti-inflammatory response in females than males. On the other hand, vitamin D has been shown to downregulate in immune cells the expression of aromatase, which converts testosterone to estrogen, leading to a decrease in estrogen level. Overall, available data allow us to hypothesize a higher protective effect of vitamin D-based therapeutic approaches in women, at least in fertile age, than in men. Future studies are needed to expand current knowledge on the immunomodulatory role of vitamin D in a sex and gender perspective, paving the way to a more personalized therapeutic approach in autoimmune diseases.

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“…Regarding VDR polymorphisms, eighteen studies that evaluated some or all FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236) VDR SNPs in MS were included in this review. Seventeen studies evaluating FokI (rs2228570) and MS were found, of which eleven studies did not find any significant association between this SNP and genetic susceptibility to MS, seven of them were case-control studies [100][101][102][103][104][105][106] and four of them were meta-analyses including overall, Asian, and Caucasian population [107][108][109][110] (Table S1).…”

Section: Multiple Sclerosis (Ms)mentioning

confidence: 99%

Association of Vitamin D Metabolism Gene Polymorphisms with Autoimmunity: Evidence in Population Genetic Studies

Ruiz-Ballesteros

Meza-Meza

Vizmanos

et al. 2020

IJMS

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A high prevalence of vitamin D (calcidiol) serum deficiency has been described in several autoimmune diseases, including multiple sclerosis (MS), rheumatoid arthritis (AR), and systemic lupus erythematosus (SLE). Vitamin D is a potent immunonutrient that through its main metabolite calcitriol, regulates the immunomodulation of macrophages, dendritic cells, T and B lymphocytes, which express the vitamin D receptor (VDR), and they produce and respond to calcitriol. Genetic association studies have shown that up to 65% of vitamin D serum variance may be explained due to genetic background. The 90% of genetic variability takes place in the form of single nucleotide polymorphisms (SNPs), and SNPs in genes related to vitamin D metabolism have been linked to influence the calcidiol serum levels, such as in the vitamin D binding protein (VDBP; rs2282679 GC), 25-hydroxylase (rs10751657 CYP2R1), 1α-hydroxylase (rs10877012, CYP27B1) and the vitamin D receptor (FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236) VDR). Therefore, the aim of this comprehensive literature review was to discuss the current findings of functional SNPs in GC, CYP2R1, CYP27B1, and VDR associated to genetic risk, and the most common clinical features of MS, RA, and SLE.

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Vitamin D receptor genetic polymorphisms and the risk of multiple sclerosis: A systematic review and meta-analysis

Cited by 24 publications

References 33 publications

Association of Vitamin D receptor gene polymorphisms and clinical/severe outcomes of COVID-19 patients

Association of Vitamin D receptor gene polymorphisms and clinical/severe outcomes of COVID-19 patients

The role of vitamin D in autoimmune diseases: could sex make the difference?

Association of Vitamin D Metabolism Gene Polymorphisms with Autoimmunity: Evidence in Population Genetic Studies

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