Cdx-2 polymorphism in the vitamin D receptor gene (VDR) marks VDR expression in monocyte/macrophages through VDR promoter methylation

Meyer, Vanessa; Bornman, Liza

doi:10.1007/s00251-018-1063-5

Cited by 16 publications

(19 citation statements)

References 39 publications

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“…Rs11568820 (Cdx2) VDR SNP was not assessed in AITD patients to date (according to the PubMed database, 31.04.2019). This SNP was previously shown to influence the immune system and modify the risk of some infectious diseases (e.g., tuberculosis and rubella) [17, 37, 38]. However, we did not observe a significant association between rs11568820 SNP and AIT risk.…”

Section: Discussioncontrasting

confidence: 94%

“…Another candidate SNP of VDR that has not been yet studied in AIT is rs11568820 (Cdx2). This functional SNP, located in the promoter region of VDR , has been found to affect the immune system [17]. Therefore, the study aimed to assess the relationship between these five VDR SNPs (rs2228570, rs1544410, rs7975232, rs731236, and rs11568820) and AIT susceptibility in the Caucasian Polish population.…”

Section: Introductionmentioning

confidence: 99%

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Vitamin D Receptor Gene Polymorphisms and Autoimmune Thyroiditis: Are They Associated with Disease Occurrence and Its Features?

Maciejewski

Kowalczyk

Herman³

et al. 2019

BioMed Research International

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Purpose. Vitamin D, besides its role in calcium-phosphorus metabolism, turned out to play a significant immunomodulating function. Until now four single nucleotide polymorphisms of vitamin D receptor gene (VDR), rs2228570 (FokI), rs1544410 (BsmI), rs7975232 (ApaI), and rs731236 (TaqI), have been studied in autoimmune thyroid disorders, with conflicting results. Another functional polymorphism of the VDR gene, rs11568820 (Cdx2), has been shown to influence the immune system, although it has not been studied for its association with autoimmune thyroiditis to date. Therefore, the study aimed to evaluate the association of these five VDR gene polymorphisms with susceptibility to autoimmune thyroiditis among Caucasian Polish population. A relationship between the studied polymorphisms and selected clinical features of the disease was additionally assessed. Methods. 223 patients with autoimmune thyroiditis and 130 control subjects were enrolled in the study. VDR polymorphisms were studied by PCR-RFLP or TaqMan real-time PCR. Results. Allele and genotype distributions of any of the studied polymorphisms did not differ significantly between patients and controls. Similarly, frequencies of haplotypes derived from rs1544410-rs7975232-rs731236 (BsmI-ApaI-TaqI) polymorphisms were not significantly different in the two studied groups. However, a weak association between rs1544410 (BsmI) or rs7975232 (ApaI) VDR polymorphisms and thyroid volume was found (p = 0.03 and p = 0.04, resp.). Conclusions. Our results suggest that VDR gene is not a major susceptibility factor for autoimmune thyroiditis development, at least in Caucasian Polish population.

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Section: Discussioncontrasting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Vitamin D Receptor Gene Polymorphisms and Autoimmune Thyroiditis: Are They Associated with Disease Occurrence and Its Features?

Maciejewski

Kowalczyk

Herman³

et al. 2019

BioMed Research International

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“…Cdx2 is considered as a functional polymorphism of the VDR gene that has been demonstrated to impact the immune system alter the risk of contracting certain infectious illnesses ( e.g. , tuberculosis and rubella) ( Meyer and Bornman, 2018 ; Ovsyannikova et al, 2010 ). Nevertheless, no substantial link has been established between this SNP and autoimmune disorders such as T1D, MS, vitiligo, or psoriasis ( Dickinson et al, 2009 ; Zhou et al, 2014 ; Frederiksen et al, 2013 ; Aydıngöz et al, 2012 ).…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, no substantial link has been established between this SNP and autoimmune disorders such as T1D, MS, vitiligo, or psoriasis ( Dickinson et al, 2009 ; Zhou et al, 2014 ; Frederiksen et al, 2013 ; Aydıngöz et al, 2012 ). Although it is uncertain why the polymorphism is connected to illnesses like tuberculosis, numerous studies have connected this association to VDR methylation, vitamin D-mediated control of chemokine-positive T cells, and impact adaptive cytokine responses ( Meyer and Bornman, 2018 ; Ovsyannikova et al, 2010 ; Harishankar and Selvaraj, 2017 ).…”

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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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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“…DNA methylation as an important epigenetic regulator plays a key role in gene expression 19 . Studies suggested that increased methylation of the VDR promoter was associated with decreased mRNA and VDR protein 20,21 . Methylation variation of the VDR promoter had been reported to be associated with cancer 20,22 .…”

Section: Introductionmentioning

confidence: 99%

Vitamin D receptor methylation attenuates the association between physical activity and type 2 diabetes mellitus: A case‐control study

Feng

et al. 2021

Journal of Diabetes

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Background Physical activity and vitamin D receptor (VDR) have been associated with type 2 diabetes mellitus (T2DM). However, the associations of VDR methylation with T2DM and physical activity remained unknown. We aimed to investigate whether VDR methylation was a link between physical activity and T2DM. Methods A 1:1 matching case‐control study was designed based on the Henan Rural Cohort Study, including 272 pairs of T2DM patients and nonpatients. Physical activity level was assessed using the International Physical Activity Questionnaire. The high‐resolution melt method was applied to determine the methylation level of the promoter region of VDR. The association between physical activity and T2DM was analyzed with a conditional logistic regression model. The effect modification of VDR methylation levels on the association between physical activity and T2DM was conducted. A multivariate correlation analysis model was applied to investigate correlations of VDR methylation with insulin sensitivity. Results Physical activity level was associated with T2DM risk (crude model: odds ratio [OR] 0.611; 95% CI, 0.416‐0.897; adjusted model: OR 0.619; 95% CI, 0.418‐0.917). In effect modification analysis, the effects of physical activity on T2DM were stronger for low VDR methylation levels than for high (P = .025). Moreover, VDR methylation levels were associated with insulin (r = −0.089, P = .039) as well as homeostatic model assessment of insulin resistance (r = −0.098, P = .022). Conclusions The methylation status of the VDR promoter is associated with the secretion and sensitivity of insulin. VDR methylation attenuates the association between physical activity and T2DM, indicating that proactively physical activity may reduce the risk of T2DM, especially in people with low VDR methylation level.

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Cdx-2 polymorphism in the vitamin D receptor gene (VDR) marks VDR expression in monocyte/macrophages through VDR promoter methylation

Cited by 16 publications

References 39 publications

Vitamin D Receptor Gene Polymorphisms and Autoimmune Thyroiditis: Are They Associated with Disease Occurrence and Its Features?

Vitamin D Receptor Gene Polymorphisms and Autoimmune Thyroiditis: Are They Associated with Disease Occurrence and Its Features?

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

Vitamin D receptor methylation attenuates the association between physical activity and type 2 diabetes mellitus: A case‐control study

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