“…Vitamin D receptor polymorphisms were associated with onset at young age or rapid onset of Japanese type 1 diabetes . Reports regarding the effect of vitamin D on diabetes in Korean pediatric adolescents are controversial; on one hand, the vitamin D receptor did not appear to affect the development of type 1 diabetes, whereas on the other hand, a protective effect was also reported …”
Background
Vitamin D metabolism has been associated with type 1 diabetes.
Objective
We aimed to clarify the association of 25‐hydroxylase (CYP2R1) and 1α‐hydroxylase (CYP27B1) with risk of developing type 1 diabetes in Korean children.
Methods
In total, 252 children (96 type 1 diabetes and 156 healthy controls) under the age of 20 years were recruited. Serum 25‐hydroxyvitamin D (25OHD) and 1α,25‐dihydroxyvitamin D [1α,25(OH)2D] levels were determined. Allelic, genotypic, and haplotypic distribution of CYP2R1 (rs12794714, rs10766196, rs10741657, rs2060793, and rs10766197) and CYP27B1 (rs4646536, rs10877012, and rs3782130) polymorphisms were determined. Clinical and biochemical data were analyzed according to genotype.
Results
Mean vitamin D level was considerably lower, and vitamin D deficiency was more prevalent in children with type 1 diabetes than in healthy controls. The GG genotype of CYP2R1 rs12794714 and AA genotype of CYP2R1 rs10766196 were significantly associated with risk of developing type 1 diabetes (odds ratio 2.00, 95% confidence interval 1.176‐3.413 and odds ratio 1.88, 95% confidence interval 1.103‐3.195, respectively). The GG+GA genotype of CYP2R1 rs12794714 and AA+AG genotype of CYP2R1 rs10766196 were associated with prevalent vitamin D deficiency in children with type 1 diabetes. These genotypes did not differ with respect to glycosylated hemoglobin and daily insulin requirement.
Conclusions
Serum 25OHD and 1α,25(OH)2D levels were lower in children with type 1 diabetes than in healthy controls. CYP2R1 rs12794714 and rs10766196 polymorphisms were associated with a higher risk of type 1 diabetes. Thus, polymorphisms in vitamin D metabolism may contribute to susceptibility to type 1 diabetes in Korean children.
“…Vitamin D receptor polymorphisms were associated with onset at young age or rapid onset of Japanese type 1 diabetes . Reports regarding the effect of vitamin D on diabetes in Korean pediatric adolescents are controversial; on one hand, the vitamin D receptor did not appear to affect the development of type 1 diabetes, whereas on the other hand, a protective effect was also reported …”
Background
Vitamin D metabolism has been associated with type 1 diabetes.
Objective
We aimed to clarify the association of 25‐hydroxylase (CYP2R1) and 1α‐hydroxylase (CYP27B1) with risk of developing type 1 diabetes in Korean children.
Methods
In total, 252 children (96 type 1 diabetes and 156 healthy controls) under the age of 20 years were recruited. Serum 25‐hydroxyvitamin D (25OHD) and 1α,25‐dihydroxyvitamin D [1α,25(OH)2D] levels were determined. Allelic, genotypic, and haplotypic distribution of CYP2R1 (rs12794714, rs10766196, rs10741657, rs2060793, and rs10766197) and CYP27B1 (rs4646536, rs10877012, and rs3782130) polymorphisms were determined. Clinical and biochemical data were analyzed according to genotype.
Results
Mean vitamin D level was considerably lower, and vitamin D deficiency was more prevalent in children with type 1 diabetes than in healthy controls. The GG genotype of CYP2R1 rs12794714 and AA genotype of CYP2R1 rs10766196 were significantly associated with risk of developing type 1 diabetes (odds ratio 2.00, 95% confidence interval 1.176‐3.413 and odds ratio 1.88, 95% confidence interval 1.103‐3.195, respectively). The GG+GA genotype of CYP2R1 rs12794714 and AA+AG genotype of CYP2R1 rs10766196 were associated with prevalent vitamin D deficiency in children with type 1 diabetes. These genotypes did not differ with respect to glycosylated hemoglobin and daily insulin requirement.
Conclusions
Serum 25OHD and 1α,25(OH)2D levels were lower in children with type 1 diabetes than in healthy controls. CYP2R1 rs12794714 and rs10766196 polymorphisms were associated with a higher risk of type 1 diabetes. Thus, polymorphisms in vitamin D metabolism may contribute to susceptibility to type 1 diabetes in Korean children.
“…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%
“…A total of 39 publications support an association between VDR SNPs rs7975232 ( ApaI ), rs1544410 ( BsmI ), rs731236 ( TaqI ) and rs10735810 ( FokI ) alone or in combination with each other, (rs757343 Tru9I , rs1540339 and rs4760648) and T1D [19,21,22,23,24,26,27,28,29,30,34,35,36,37,38,40,41,42,43,44,46,48,49,50,52,53,55,56,59,60,61,62,63,65,68,69,70,71,73] (Table 2) in comparison with 16 studies that refute it [20,25,31,32,39,45,47,51,54,57,58,64,66,67,72,74]. …”
Section: Vitamin D Pathwaysmentioning
confidence: 99%
“…Furthermore, a variety of VDR allele combinations have been described as T1D protective [21,24,38,48,49,50,63,69,70]. …”
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.
“…After screening the titles and abstracts, 41 studies were excluded because they were not considered relevant to the study topic, leaving 9 potentially eligible studies (Fig. 1) (15, 16, 17, 18, 19, 20, 21, 22, 23). Figure 1Flow chart for identification and selection of studies.
…”
BackgroundThere 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.MethodsThis 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.ResultsA 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.ConclusionThe 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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