Vitamin D receptor initiation codon polymorphism influences genetic susceptibility to type 1 diabetes mellitus in the Japanese population

Ban, Yoshiyuki; Taniyama, Matsuo; Yanagawa, Tatsuo; Yamada, Satoru; Maruyama, Taro; Kasuga, Akira; Ban, Yoshio

doi:10.1186/1471-2350-2-7

Cited by 79 publications

(60 citation statements)

References 64 publications

(90 reference statements)

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“…LRP5 is a member of the low-density lipoprotein receptor family that is expressed in cells of the mononuclear-phagocyte system, the islets of Langerhans, vitamin A-metabolising cells, and CNS neurons [131]. Vitamin D receptor polymorphisms have been associated with risk for type 1A diabetes in several populations [132,133,134,135].…”

Section: Other Genes and Locimentioning

confidence: 99%

Genetic control of autoimmunity in Type I diabetes and associated disorders

2002

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Type I (insulin-dependent) diabetes mellitus is a heterogeneous disease with major subdivisions termed Type 1A (immune-mediated) and Type 1B. Immunemediated diabetes is also heterogeneous with ªmono-genicº, oligogenic, and polygenic forms present in humans and in animal models. Single-gene mutations of two transcription factors have been recently identified in rare syndromes of autoimmunity with type 1A diabetes: autoimmune polyendocrine syndrome type 1 (APS-1) and X-linked polyendocrinopathy, immune dysfunction and diarrhoea (XPID). For more common forms of diabetes, susceptibility loci within the major histocompatibility complex and at the insulin locus have been identified. Both DQ* and DR* alleles provide susceptibility and certain alleles dominant protection. In the Diabetes Autoimmunity Study of the Young approximately 50 % of the siblings studied with the highest-risk HLA genotype develop anti-islet autoantibodies by age 3. Insulin could be a crucial autoantigen related to genetic susceptibility. The crystal structure of the high-risk allele, HLA-DQ8, complexed with an insulin peptide has just been reported. Insulin production by macrophage-dendritic cells within the thymus and lymphoid organs could underlie insulin gene polymorphisms influencing the risk of diabetes. Genome-wide scans for linkage in animal models and in humans have not conclusively identified other susceptibility genes though many loci have been implicated. We favour the hypothesis that HLA is a major determinant of susceptibility in animal models and in most families, and that the search for diabetogenes should concentrate on unique families to decrease heterogeneity and favour the eventual discovery of genes influencing risk. [Diabetologia (2002) 45:605±622]

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Section: Other Genes and Locimentioning

confidence: 99%

Genetic control of autoimmunity in Type I diabetes and associated disorders

2002

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“…Observations in animal models suggest the latter, since regular supplements of vitamin D in neonatal and early life offered no protection against type 1 diabetes in nonobese diabetic (NOD) mice or in BioBreeding (BB) rats [56,57], whereas the prevalence of diabetes is doubled in NOD mice rendered vitamin D-deficient in early life [58,59]. The results of genetic studies investigating a possible relationship between VDR polymorphisms and type 1 diabetes are highly confusing: a clear correlation exist in some populations [60][61][62][63][64][65], whereas no correlation can be found in others [66].…”

Section: Vitamin D and Type 1 Diabetesmentioning

confidence: 99%

Vitamin D and diabetes

et al. 2005

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Vitamin D deficiency predisposes individuals to type 1 and type 2 diabetes, and receptors for its activated form-1α,25-dihydroxyvitamin D 3 -have been identified in both beta cells and immune cells. Vitamin D deficiency has been shown to impair insulin synthesis and secretion in humans and in animal models of diabetes, suggesting a role in the development of type 2 diabetes. Furthermore, epidemiological studies suggest a link between vitamin D deficiency in early life and the later onset of type 1 diabetes. In some populations, type 1 diabetes is associated with certain polymorphisms within the vitamin D receptor gene. In studies in nonobese diabetic mice, pharmacological doses of 1α,25-dihydroxyvitamin D 3 , or its structural analogues, have been shown to delay the onset of diabetes, mainly through immune modulation. Vitamin D deficiency may, therefore, be involved in the pathogenesis of both forms of diabetes, and a better understanding of the mechanisms involved could lead to the development of preventive strategies.

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“…VDR has been shown to be present in significant concentrations in T lymphocytes and macrophages (19), and some of its polymorphisms have recently been found to be associated with several autoimmune diseases in man, such as psoriasis (20), Grave's disease (21,22), Addison's disease (23) and T1D (24 -31). In addition, the VDRF and VDRB single nucleotide polymorphisms (SNPs) were suggested to have an effect on GAD65-autoantibody positivity in T1D (30) and on the onset pattern of the disease (31), respectively, in Japanese case-control analyses.…”

Section: Introductionmentioning

confidence: 99%

Vitamin D receptor polymorphisms: no association with type 1 diabetes in the Finnish population

Turpeinen

Hermann

Vaara

et al. 2003

European Journal of Endocrinology

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Objective: The effect of polymorphisms of the vitamin D receptor (VDR) gene on susceptibility to type 1 diabetes has recently been investigated extensively. Several findings on positive disease associations have been observed and, in addition, a protective effect of vitamin D supplementation has been reported. Design: We studied the effect of three vitamin D receptor gene polymorphisms (VDRA, VDRB, VDRF) on susceptibility to type 1 diabetes in a large case-control series (more than 2000 controls and about 1000 patients) from the Finnish population. Methods: A combination of case-control and affected-family based approaches was used. Subjects were genotyped for VDRA (ApaI), VDRB (BsmI) and VDRF (FokI) single nucleotide polymorphisms using a minisequencing reaction. Results: A few borderline significant associations were observed with both approaches used. In the case-control association analyses we found significant differences between cases and controls in frequencies of VDRB (P ¼ 0.024, all subjects and P ¼ 0.016, HLA DQB1 * 0302-positive subjects) and VDRF (P ¼ 0.0063, Turku cohort). In the total family set a decreased (39.3%) transmission of the VDRA-VDRB-VDRF haplotype 1-1-2 and an increased (60.3%) transmission of haplotype 2-1-2 to sons was seen (P ¼ 0.0059 and P ¼ 0.024 respectively). Transmission of the haplotype 2-2-1 to daughters was decreased (37.6%, P ¼ 0.022). Interestingly, we also observed significant differences in allele frequencies of the polymorphisms studied between populations from three different regions in Finland. Conclusions: All these differences disappeared after correction for multiple testing. We conclude that the single nucleotide polymorphisms analysed are unlikely to be associated with type 1 diabetes in the Finnish population.

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Vitamin D receptor initiation codon polymorphism influences genetic susceptibility to type 1 diabetes mellitus in the Japanese population

Cited by 79 publications

References 64 publications

Genetic control of autoimmunity in Type I diabetes and associated disorders

Genetic control of autoimmunity in Type I diabetes and associated disorders

Vitamin D and diabetes

Vitamin D receptor polymorphisms: no association with type 1 diabetes in the Finnish population

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