Vitamin D receptor polymorphisms: are they really associated with type 1 diabetes?

Bianco, Maria Giovanna; Minicucci, L.; Calevo, Maria Grazia; Lorini, Renata

doi:10.1530/eje.0.1510641

Cited by 14 publications

(12 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Individual VDR polymorphisms have been studied in different populations with conflicting reports. Some reports find a positive association of VDR polymorphism with T1D [41]–[46], while there are a considerable number of reports where no association of VDR polymorphism with T1D was observed [47]–[49]. In a meta-analysis Guo et al [50] did not see any evidence of significant association between VDR polymorphism and T1D in either case-control or family transmission.…”

Section: Discussionmentioning

confidence: 96%

Interaction of Vitamin D Receptor with HLA DRB1*0301 in Type 1 Diabetes Patients from North India

et al. 2009

View full text Add to dashboard Cite

BackgroundType 1 diabetes (T1D) is a multifactorial autoimmune disorder where interaction and integration of immune response genes along with environmental factors play a role in autoimmune destruction of the insulin producing Pancreatic Beta cells.Methodology/Principal FindingsWe have studied four single nucleotide polymorphisms (FokI site in Exon 2, BsmI and ApaI sites in Intron 8 and TaqI site in exon 9) in the vitamin D receptor (VDR) gene using PCR-RFLP and HLA-DRB1 alleles using PCR and hybridization with sequence specific oligonucleotide probes and studied their interaction using LD based statistics for non-linked loci followed by sequence analysis of the vitamin D response element (VDRE) present in the promoter region of HLA-DRB1*0301. Haplotypes, constructed using SHEsis program for four single nucleotide polymorphisms in the VDR gene, were studied for their interaction with HLA-DRB1 alleles in 233 T1D patients and 191 healthy controls from North India. A significant increase of haplotypes FBAt and fBAT (p<0.02, OR = 1.44 and p<0.002, OR = 3.23 respectively) was observed in the patients. Both the haplotypes FBAt and fBAT were significantly increased in male patients with age at onset less than 18 years; however, fBAT was significantly increased in female patients irrespective of their age at onset. LD based statistics showed significant interaction between the high producer F and T alleles with HLA-DRB1*0301. F and T alleles of VDR have been shown to contribute to VDR mRNA independently. The promoter sequence analysis of HLA-DRB1*0301 showed presence of VDRE involved in higher expression of HLA-DRB1*030, which was confirmed by flow cytometry and real time PCR analysis.Conclusions/SignificanceThese data suggest that the interaction between VDR and HLA alleles is mediated by VDRE present in the promoter region of HLA-DRB1*0301 allele, which may be detrimental for the manifestation of T1D in the absence of 1,25-(OH)2D3 in early childhood due to poor expression of DRB1*0301 in the thymus resulting in autoimmunity.

show abstract

Section: Discussionmentioning

confidence: 96%

Interaction of Vitamin D Receptor with HLA DRB1*0301 in Type 1 Diabetes Patients from North India

et al. 2009

View full text Add to dashboard Cite

show abstract

“…In humans, retrospective analysis and observational studies demonstrated high prevalence of 25-OH D deficiency in patients with T1DM [61–68] and suggested a contributory role in the pathogenesis of T1DM, specially with certain allelic variations of the VDR [32–57]. Conversely, vitamin D supplementation during pregnancy and early childhood decreased the risk of autoimmune diabetes [96–104] and perhaps, even after the onset of diabetes, it may improve glycemic control [114, 115].…”

Section: Discussionmentioning

confidence: 99%

“…Five single nucleotide polymorphisms (SNP) in exon 2 ( Fok I), intron 8 ( Bsm I, Tru9 I, Apa I), and exon 9 ( Taq I) have been defined historically in VDR gene, by the associated restriction enzyme [31]. Association studies of VDR allelic variations and T1D done in many countries, including different populations (southern [32] and northern [33] India, Iran [34], Spain [35], Romania [36, 37], Turkey [38, 39], Hungary [40], Portugal [41], UK, US, Norway [42], Japan [42, 43], Finland [42, 44], Poland [45], Croatia [46, 47], Brazil [48], Uruguay [49], Germany [50–52], Greece [53], Bangladesh [54], Taiwan [55], Chile [56], and Italy [57]) yielded conflicting results; some showed significant association while others failed to reach statistical significance, as shown in Table 1. These different results may be related to differences in ethnic background of the populations studied, interactions with other genetic or environmental factors involved in the pathogenesis of T1DM [34], and possibly differences in ultraviolet radiation exposure [58].…”

Section: Vitamin D Polymorphismmentioning

confidence: 99%

The Role of Vitamin D Deficiency in the Incidence, Progression, and Complications of Type 1 Diabetes Mellitus

Chakhtoura

Azar

2013

International Journal of Endocrinology

View full text Add to dashboard Cite

The “nonclassic” role of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) has been recently widely recognized. In type 1 diabetes mellitus (T1D), it plays an immunomodulatory role through the vitamin D receptor (VDR) present on pancreatic and immune cells. Specific VDR allelic variants have been associated with T1D in many countries. Furthermore, vitamin D deficiency has been prevalent in T1D, and the seasonal and latitude variability in the incidence of T1D can be partly explained by the related variability in vitamin D level. In fact, retrospective studies of vitamin D supplementation during pregnancy or infancy showed a lower incidence of T1D. We will review the different mechanisms of the vitamin D protective effect against insulitis and present the available data on the role of vitamin D deficiency in the control, progression, and complications of T1D.

show abstract

“…To date, there are 65 publications [19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83] on the association of VDR gene SNPs in T1D: these include case-control datasets [20,22,23,25,26,27,28,…”

Section: Vitamin D Pathwaysmentioning

confidence: 99%

Inherited Variation in Vitamin D Genes and Type 1 Diabetes Predisposition

Penna-Martinez

Badenhoop

2017

Genes

View full text Add to dashboard Cite

The etiology and pathophysiology of type 1 diabetes remain largely elusive with no established concepts for a causal therapy. Efforts to clarify genetic susceptibility and screening for environmental factors have identified the vitamin D system as a contributory pathway that is potentially correctable. This review aims at compiling all genetic studies addressing the vitamin D system in type 1 diabetes. Herein, association studies with case control cohorts are presented as well as family investigations with transmission tests, meta-analyses and intervention trials. Additionally, rare examples of inborn errors of vitamin D metabolism manifesting with type 1 diabetes and their immune status are discussed. We find a majority of association studies confirming a predisposing role for vitamin D receptor (VDR) polymorphisms and those of the vitamin D metabolism, particularly the CYP27B1 gene encoding the main enzyme for vitamin D activation. Associations, however, are tenuous in relation to the ethnic background of the studied populations. Intervention trials identify the specific requirements of adequate vitamin D doses to achieve vitamin D sufficiency. Preliminary evidence suggests that doses may need to be individualized in order to achieve target effects due to pharmacogenomic variation.

show abstract

Vitamin D receptor polymorphisms: are they really associated with type 1 diabetes?

Cited by 14 publications

References 5 publications

Interaction of Vitamin D Receptor with HLA DRB1*0301 in Type 1 Diabetes Patients from North India

Interaction of Vitamin D Receptor with HLA DRB1*0301 in Type 1 Diabetes Patients from North India

The Role of Vitamin D Deficiency in the Incidence, Progression, and Complications of Type 1 Diabetes Mellitus

Inherited Variation in Vitamin D Genes and Type 1 Diabetes Predisposition

Contact Info

Product

Resources

About