Vitamin D receptor polymorphism and susceptibility to type 1 diabetes in chilean subjects: A case-parent study

Ángel, Bárbara; Santos, José Luis; Carrasco, Elena; Albala, Cecilia; Pérez-Bravo, Francisco

doi:10.1007/s10654-004-1026-z

Cited by 29 publications

(25 citation statements)

References 22 publications

(24 reference statements)

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“…In the German and Croatian populations BAt haplotype the strongest susceptibility combination was found. On the other hand, Finnish and Chilean population studies did not support the claim of a significant genetic effect of VDR alleles in the etiology of T1D 25,26 . A meta-analysis concerning the relation between T1D and VDR polymorphisms found no evidence for an association between BsmI, ApaI and TaqI VDR polymorphisms and the risk of developing T1D 27 .…”

Section: Discussionmentioning

confidence: 80%

Effects of Vitamin D Receptor Gene Polymorphisms on Susceptibility to Disease and Bone Mineral Density in Turkish Patients with Type 1 Diabetes Mellitus

Kocabaş

Karagüzel

İmir

et al. 2010

Journal of Pediatric Endocrinology and Metabolism

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Background: Vitamin D receptor (VDR) gene is regarded as one of the candidate genes for type 1 diabetes mellitus (T1D) susceptibility and of some genetic factors involved in the development of osteoporosis in this group. Study design: We characterized the VDR gene polymorphism (BsmI, ApaI, TaqI, FokI and Cdx-2 binding site) in a group of Turkish patients with T1D (n=90) and correlated respective VDR genotypes with the bone mass and some parameters of bone turnover. Results: There were no differences in the genotype frequencies of the BsmI, ApaI, TaqI and Cdx-2 polymorphisms in patients and control subjects. We found a significantly higher prevalence of the F allele/the FF genotype in the patients compared to controls (p=0,0031, odds 1. 96 (1,27-3,01)). We observed no difference in markers of bone turnover (Serum levels of osteocalcin, PINP and alkaline phosphatase, urinary levels of calcium/ creatinine and N-telopeptid) among different VDR genotypes. No correlation was found between VDR polymorphisms and DEXA measurements of these patients. Conclusions: Although the FF genotype was found to be a risk factor in a Turkish population, elucidation of this result is necessary in other larger study groups drawn from the same ethnic population.

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Section: Discussionmentioning

confidence: 80%

Effects of Vitamin D Receptor Gene Polymorphisms on Susceptibility to Disease and Bone Mineral Density in Turkish Patients with Type 1 Diabetes Mellitus

Kocabaş

Karagüzel

İmir

et al. 2010

Journal of Pediatric Endocrinology and Metabolism

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“…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: 95%

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

et al. 2009

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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.

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“…VDR 2228570 has been inconsistently associated with T1D [10,22,26,39–45]. VDR rs2228570 is a coding non-synonymous SNP located in the translational initiation codon that determines the formation of two protein variants: a longer version of the VDR protein (427-amino acids) that corresponds to the A allele and a form shortened by three amino acids corresponding to the G allele (424-amino acids) [23,46,47].…”

Section: Discussionmentioning

confidence: 99%

Investigation of the vitamin D receptor gene (VDR) and its interaction with protein tyrosine phosphatase, non-receptor type 2 gene (PTPN2) on risk of islet autoimmunity and type 1 diabetes: The Diabetes Autoimmunity Study in the Young (DAISY)

Frederiksen

Liu²,

Romanos

et al. 2013

The Journal of Steroid Biochemistry and Molecular Biology

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The present study investigated the association between variants in the vitamin D receptor gene (VDR) and protein tyrosine phosphatase, non-receptor type 2 gene (PTPN2), as well as an interaction between VDR and PTPN2 and the risk of islet autoimmunity (IA) and progression to type 1 diabetes (T1D). The Diabetes Autoimmunity Study in the Young (DAISY) has followed children at increased risk of T1D since 1993. Of the 1692 DAISY children genotyped for VDR rs1544410, VDR rs2228570, VDR rs11568820, PTPN2 rs1893217, and PTPN2 rs478582, 111 developed IA, defined as positivity for GAD, insulin or IA-2 autoantibodies on 2 or more consecutive visits, and 38 IA positive children progressed to T1D. Proportional hazards regression analyses were conducted. There was no association between IA development and any of the gene variants, nor was there evidence of a VDR*PTPN2 interaction. Progression to T1D in IA positive children was associated with the VDR rs2228570 GG genotype (HR: 0.49, 95% CI: 0.26–0.92) and there was an interaction between VDR rs1544410 and PTPN2 rs1893217 (pinteraction = 0.02). In children with the PTPN2 rs1893217 AA genotype, the VDR rs1544410 AA/AG genotype was associated with a decreased risk of T1D (HR: 0.24, 95% CI: 0.11–0.53, p = 0.0004), while in children with the PTPN2 rs1893217 GG/GA genotype, the VDR rs1544410 AA/AG genotype was not associated with T1D (HR: 1.32, 95% CI: 0.43–4.06, p = 0.62). These findings should be replicated in larger cohorts for confirmation. The interaction between VDR and PTPN2 polymorphisms in the risk of progression to T1D offers insight concerning the role of vitamin D in the etiology of T1D.

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Vitamin D receptor polymorphism and susceptibility to type 1 diabetes in chilean subjects: A case-parent study

Cited by 29 publications

References 22 publications

Effects of Vitamin D Receptor Gene Polymorphisms on Susceptibility to Disease and Bone Mineral Density in Turkish Patients with Type 1 Diabetes Mellitus

Effects of Vitamin D Receptor Gene Polymorphisms on Susceptibility to Disease and Bone Mineral Density in Turkish Patients with Type 1 Diabetes Mellitus

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

Investigation of the vitamin D receptor gene (VDR) and its interaction with protein tyrosine phosphatase, non-receptor type 2 gene (PTPN2) on risk of islet autoimmunity and type 1 diabetes: The Diabetes Autoimmunity Study in the Young (DAISY)

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