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      Association of vitamin D receptor polymorphisms and type 1 diabetes susceptibility in children: a meta-analysis

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          Abstract

          Background

          There have been studies focused on FokI, BsmI, ApaI and TaqI polymorphisms of the vitamin D receptor (VDR) gene and susceptibility to type 1 diabetes mellitus with controversial results.

          Methods

          This present study is a meta-analysis investigating the association between FokI, ApaI, TaqI and BsmI polymorphisms of VDR gene and type 1 DM in children. A literature search was performed using Medline, EMBASE, Cochrane and PubMed. Any study was considered eligible for inclusion if at least one of FokI, ApaI, TaqI and BsmI polymorphisms was determined, and outcome was type 1 DM at pediatric age.

          Results

          A total of 9 studies comprising 1053 patients and 1017 controls met the study inclusion criteria. The pooled odds ratios (ORs) of the FokI, ApaI, TaqI and BsmI polymorphisms were combined and calculated. Forest plots and funnel plots of the OR value distributions were drawn. Our meta-analysis has demonstrated statistically significant associations between DM1 and VDR genotypes, BsmIBB ( P < 0.05), BsmIBb, ( P < 0.05), BsmIbb ( P < 0.05), TaqITT ( P < 0.05) and TaqItt ( P < 0.05) in children.

          Conclusion

          The results indicated that BsmIBB, BsmIBb and TaqItt polymorphisms were associated with an increased risk of type 1 DM, whereas BsmIbb and TaqITT had protective effect for type 1 DM in children.

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          Most cited references34

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          HLA-DQ beta gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus.

          Over half of the inherited predisposition to insulin-dependent diabetes mellitus maps to the region of chromosome 6 that contains the highly polymorphic HLA class II genes which determine immune responsiveness. Analysis of DNA sequences from diabetics indicates that alleles of HLA-DQ beta determine both disease susceptibility and resistance, and that the structure of the DQ molecule, in particular residue 57 of the beta-chain, specifies the autoimmune response against the insulin-producing islet cells.
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            Inherited Variation in Vitamin D Genes Is Associated With Predisposition to Autoimmune Disease Type 1 Diabetes

            OBJECTIVE Vitamin D deficiency (25-hydroxyvitamin D [25(OH)D] <50 nmol/L) is commonly reported in both children and adults worldwide, and growing evidence indicates that vitamin D deficiency is associated with many extraskeletal chronic disorders, including the autoimmune diseases type 1 diabetes and multiple sclerosis. RESEARCH DESIGN AND METHODS We measured 25(OH)D concentrations in 720 case and 2,610 control plasma samples and genotyped single nucleotide polymorphisms from seven vitamin D metabolism genes in 8,517 case, 10,438 control, and 1,933 family samples. We tested genetic variants influencing 25(OH)D metabolism for an association with both circulating 25(OH)D concentrations and disease status. RESULTS Type 1 diabetic patients have lower circulating levels of 25(OH)D than similarly aged subjects from the British population. Only 4.3 and 18.6% of type 1 diabetic patients reached optimal levels (≥75 nmol/L) of 25(OH)D for bone health in the winter and summer, respectively. We replicated the associations of four vitamin D metabolism genes (GC, DHCR7, CYP2R1, and CYP24A1) with 25(OH)D in control subjects. In addition to the previously reported association between type 1 diabetes and CYP27B1 (P = 1.4 × 10−4), we obtained consistent evidence of type 1 diabetes being associated with DHCR7 (P = 1.2 × 10−3) and CYP2R1 (P = 3.0 × 10−3). CONCLUSIONS Circulating levels of 25(OH)D in children and adolescents with type 1 diabetes vary seasonally and are under the same genetic control as in the general population but are much lower. Three key 25(OH)D metabolism genes show consistent evidence of association with type 1 diabetes risk, indicating a genetic etiological role for vitamin D deficiency in type 1 diabetes.
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              Genetic analysis of autoimmune disease.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                April 2017
                23 February 2017
                : 6
                : 3
                : 159-171
                Affiliations
                [1 ]Department of Pediatrics Acıbadem University School of Medicine, Atasehir, Istanbul, Turkey
                [2 ]Department of Pediatric Endocrinology Faculty of Medicine, Ege University, Bornova, Izmir, Turkey
                [3 ]Department of Biochemistry Acıbadem University, School of Medicine, Atasehir, Istanbul, Turkey
                [4 ]Department of Medical Genetics Faculty of Medicine, Ege University, Bornova, Izmir, Turkey
                Author notes
                Correspondence should be addressed to O A Sahin; Email: ozlemnaciyeatansahin@ 123456yahoo.com
                Article
                EC160110
                10.1530/EC-16-0110
                5424779
                28232367
                15a1d912-455c-42b7-b46c-b109a344019b
                © 2017 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License..

                History
                : 13 February 2017
                : 23 February 2017
                Categories
                Research

                vdr,diabetes mellitus,polymorphisms,meta-analysis
                vdr, diabetes mellitus, polymorphisms, meta-analysis

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