Vitamin D receptor (VDR) gene polymorphism and risk of rheumatoid arthritis (RA): systematic review and meta-analysis

Bagheri‐Hosseinabadi, Zahra; Imani, Danyal; Yousefi, Hassan; Abbasifard, Mitra

doi:10.1007/s10067-020-05143-y

Cited by 32 publications

(27 citation statements)

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“…76 Specifically, in this cohort, VDR Fok1-f allele was found in 82% of participants, and is reported to be associated with downregulating T helper type 1 (Th1) immune response (ie, cells that secrete TNF-α and cytokine interferon γ). 76 77 Possibly, VDR gene polymorphisms are linked to chronic inflammation, 78 which may play a role in high BP. In a matched casecontrol study of 280 adults with hypertension, compared with normotensive controls, genotypes of VDR FokI polymorphisms (ie, 'FF' and 'Ff' vs 'ff' genotypes) show that the odds of hypertension were significantly higher for the Table 2 Adjusted marginal structural models estimating controlled direct effects (CDE) of inflammatory markers (i.e., highsensitivity C reactive protein (CRP), tumour necrosis factor (TNF), and Interleukin 6 (IL-6)) on systolic blood pressure (SBP) measures in the presence and absence of vitamin D (VD) insufficiency [25(OH) Open access FF genotype and allele F. 79 In contrast, a prospective study of men without hypertension shows the risk of hypertension was higher for ff genotype carriers of FokI polymorphisms compared with FF and Ff genotypes combined.…”

Section: Discussionmentioning

confidence: 99%

Examining chronic inflammatory markers on blood pressure measures in the presence of vitamin D insufficiency among indigenous cree adults: results from the cross-sectional Multi-Community Environment-and-Health Study inEeyou Istchee, Quebec, Canada

Zuk

Tsuji

2021

BMJ Open

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ObjectiveHigh blood pressure (BP) is a risk factor for cardiovascular disease. Examining the role of inflammatory mediators on BP is important since vitamin D (VD) is a modifiable risk factor, which possibly modulates inflammatory cytokines. This study simulated what are known as average ‘controlled direct effects (CDE)’ of inflammatory markers, C reactive protein (CRP), tumour necrosis factor-α (TNF-α), and interlukin-6 (IL-6) on continuous BP measures, while fixing VD, an intermediate variable to specific level.DesignCross-sectional study.SettingWe analysed data from the Multi-Community Environment-and-Health Study, 2005–2009, conducted in Eeyou Istchee, Quebec, Canada.ParticipantsThis study recruited 1425 study Indigenous Cree participants from seven Cree communities. Only adults with serum VD levels, inflammatory markers and BP measures were included in this data analysis.Primary and secondary outcomes measuresInflammatory markers examined the top 25th exposure percentiles. VD ‘insufficiency’ (ie, 25-hydroxyvitamin-D levels<50 nmol/L) defined by the Institute of Medicine. CDE for each inflammatory marker in the presence and absence of population VD insufficiency simulated the average direct effect change for systolic and diastolic BP (SBP and DBP) measures. All models were adjusted for exposure-and-mediator outcome relationship.ResultsAmong 161 participants, 97 (60 %) were female. The prevalence of VD insufficiency was 32%. CDE estimates show in the presence and absence of population vitamin D insufficiency, inflammatory markers have a slightly different association on BP. TNF-α significantly and inversely associated with SBP in the presence of vitamin D insufficiency, fully adjusted model β = −13.61 (95% CI −24.42 to −2.80); however, TNF-α was not associated with SBP in the absence of vitamin D insufficiency. CRP, IL-6 were also not significantly associated with BP measures, although the magnitude of association was greater for those with elevated inflammation and VD insufficiency.ConclusionThis novel analysis shows in the presence of VD insufficiency, inflammation (particularly TNF-α) may affect SBP. Additional research is needed to elucidate these findings, and the temporal relationship between these variables.

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Section: Discussionmentioning

confidence: 99%

Examining chronic inflammatory markers on blood pressure measures in the presence of vitamin D insufficiency among indigenous cree adults: results from the cross-sectional Multi-Community Environment-and-Health Study inEeyou Istchee, Quebec, Canada

Zuk

Tsuji

2021

BMJ Open

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“…Vitamin D (VitD) is a steroid molecule that has many roles in the body, such as regulation of the immune cells. In addition to immune responses, VitD is also involved in the etiopathogenesis of several disorders, such as cancer, autoimmune disorders, cardiovascular disorders, asthma, and diabetes [6][7][8][9]. In animal model of T1DM, VitD suppresses the occurrence of diabetes, by regulating the T helper (Th) 1/Th2 cytokine balance in the local pancreatic lesions [10,11].…”

Section: Introductionmentioning

confidence: 99%

Vitamin D receptor gene polymorphisms and the risk of the type 1 diabetes: a meta-regression and updated meta-analysis

et al. 2020

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Background: The association between the polymorphisms in the vitamin D receptor (VDR) gene and the risk of type 1 diabetes mellitus (T1DM) has been evaluated in several studies. However, the findings were inconclusive. Thus, we conducted a meta-analysis to comprehensively evaluate the effect of VDR gene polymorphisms on the risk of T1DM. Methods: All relevant studies reporting the association between VDR gene polymorphisms and susceptibility to T1DM published up to May 2020 were identified by comprehensive systematic database search in ISI Web of Science, Scopus, and PubMed/MEDLINE. Strength of association were assessed by calculating of pooled odds ratios (ORs) and 95% confidence intervals (CIs). The methodological quality of each study was assessed according to the Newcastle-Ottawa Scale. To find the potential sources of heterogeneity, meta-regression and subgroup analysis were also performed. Results: A total of 39 case-control studies were included in this meta-analysis. The results of overall population rejected any significant association between VDR gene polymorphisms and T1DM risk. However, the pooled results of subgroup analysis revealed significant negative and positive associations between FokI and BsmI polymorphisms and T1DM in Africans and Americans, respectively. Conclusions: This meta-analysis suggested a significant association between VDR gene polymorphism and T1DM susceptibility in ethnic-specific analysis.

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“…The VDR FokI polymorphism was associated with intervertebral disc degeneration among Caucasians but not Asians [9]. Moreover, different VDR polymorphisms exerted opposite effects on susceptibility to rheumatoid arthritis in different populations [8]. Inconsistent findings in studies could also be a result of the criteria applied for OA patients' inclusion, clinical heterogeneity, age or gender discrepancies among cases and controls, and the differences in affected jointtypes, weight-bearing joints, such as knees and hips, as opposed to other joints [4,25].…”

Section: Discussionmentioning

confidence: 90%

“…Calcitriol (1,25-dihydroxyvitamin D3, 1,25(OH)2D3), a bioactive form of vitamin D, is a steroid hormone known for its central role in bone mineralization and basal serum calcium and phosphorus level maintenance. Also, vitamin D3 exerts diverse immunomodulatory and antiinflammatory effects [7][8][9][10]. The biological effects of vitamin D3 are mediated through binding to the vitamin D receptor (VDR), which acts as a ligand-activated transcription factor.…”

Section: Introductionmentioning

confidence: 99%

“…The biological effects of vitamin D3 are mediated through binding to the vitamin D receptor (VDR), which acts as a ligand-activated transcription factor. Several VDR gene polymorphisms have a functional immunomodulatory impact [7] and influence rheumatoid arthritis risk [8] and intervertebral disc degeneration [9] in different populations and could therefore play a significant role in the pathogenesis of OA. About 500 single nucleotide polymorphisms (SNPs) in the human VDR gene have been described so far, and the most extensively studied variants are FokI, TaqI, ApaI, and EcoRV [11].…”

Section: Introductionmentioning

confidence: 99%

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Vitamin D receptor gene variants contribute to hip and knee osteoarthritis susceptibility

Vranic

Zeljić

Štefik

et al. 2021

ARCH BIOL SCI BELGRA

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Vitamin D receptor (VDR) gene polymorphisms could play a significant role in the susceptibility and pathogenesis of osteoarthritis (OA), the most common degenerative joint disorder in humans. The current study involved 94 OA patients and 100 healthy, asymptomatic controls. VDR variants FokI (rs2228570), TaqI (rs731236), ApaI (rs7975232) and EcoRV (rs4516035) were genotyped using TaqMan-based real-time PCR. Adjusted odds ratio (OR) analysis showed that VDR TaqI and FokI polymorphisms are significantly associated with susceptibility to OA (OR=1.986, P=0.001 and OR=1.561, P=0.017, respectively). Joint-specific analysis showed that the VDR TaqI polymorphism was associated with risk of hip OA (OR=1.930, P=0.005) and knee OA (OR=1.916, P=0.028), while the VDR FokI polymorphism was associated with higher risk of knee OA (OR=2.117, P=0.012). VDR TaqI and FokI polymorphisms are associated with the occurrence of persistent pain (P=0.005 and P=0.027, respectively), while ApaI was associated with a family history of OA (p=0.004). The VDR FokI and TaqI genetic variants significantly contribute to osteoarthritis susceptibility, the occurrence of persistent pain, and potentially to joint-specific OA risk.

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Vitamin D receptor (VDR) gene polymorphism and risk of rheumatoid arthritis (RA): systematic review and meta-analysis

Cited by 32 publications

References 54 publications

Examining chronic inflammatory markers on blood pressure measures in the presence of vitamin D insufficiency among indigenous cree adults: results from the cross-sectional Multi-Community Environment-and-Health Study inEeyou Istchee, Quebec, Canada

Examining chronic inflammatory markers on blood pressure measures in the presence of vitamin D insufficiency among indigenous cree adults: results from the cross-sectional Multi-Community Environment-and-Health Study inEeyou Istchee, Quebec, Canada

Vitamin D receptor gene polymorphisms and the risk of the type 1 diabetes: a meta-regression and updated meta-analysis

Vitamin D receptor gene variants contribute to hip and knee osteoarthritis susceptibility

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