Allelic variation in the vitamin D receptor influences susceptibility to IDDM in Indian Asians

McDermott, Michael F.; Ramachandran, Ambady; Ogunkolade, B; Aganna, Ebun; Curtis, David; Boucher, Barbara J.; Snehalatha, Chamukuttan; Hitman, G. A.

doi:10.1007/s001250050776

Cited by 155 publications

(116 citation statements)

References 36 publications

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“…In particular, a cohort study determining the intake of vitamin D and serum concentrations of 25-hydroxyvitamin D 3 would be helpful. The epidemiological surveys performed so far have not taken into account the gene polymorphism for the vitamin D receptor or another gene involved in vitamin D metabolism, which might be linked to type 1 diabetes [29][30][31][32].…”

Section: Discussionmentioning

confidence: 99%

Maternal intake of vitamin D during pregnancy and risk of advanced beta cell autoimmunity and type 1 diabetes in offspring

et al. 2010

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Section: Discussionmentioning

confidence: 99%

Maternal intake of vitamin D during pregnancy and risk of advanced beta cell autoimmunity and type 1 diabetes in offspring

et al. 2010

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“…In diabetic patients from India, the bAT allele indicated an increased risk, whereas the same allele was considered to be protective in German patients. 36,37 Several studies investigating the association between bone mass and VDR polymorphisms also reported inverse associations with disease susceptibility. 31,33,56,57 These findings are likely to be influenced by genetic heterogeneity that exists for VDR gene polymorphisms in different diseases as well as in evolutionary divergent populations.…”

Section: Discussionmentioning

confidence: 99%

“…[31][32][33][34][35] However, analyses of autoimmune diseases have recently led to the discovery of an association of VDR polymorphisms with diabetes mellitus in patients from different ethnic backgrounds, including Taiwanese, Indian, and German individuals. [36][37][38] Additional studies have described a genetic link with multiple sclerosis and Grave's disease. [39][40][41][42] Springer et al identified VDR polymorphisms as an independent genetic risk factor of decreased bone mineral density in PBC and found a significant different frequency of VDR polymorphisms in PBC patients compared with a local control population.…”

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confidence: 99%

Genetic association of vitamin D receptor polymorphisms with primary biliary cirrhosis and autoimmune hepatitis

2002

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Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) are immune-mediated chronic inflammatory diseases of the liver of unknown etiology. Genetic factors appear to be involved in the pathogenesis of both diseases. 1,25-Dihydroxyvitamin D 3 has been implicated as an immunomodulator, which acts through its own receptor (VDR). Polymorphisms of the VDR have been linked to a variety of autoimmune diseases. In this study VDR polymorphisms were analyzed in 123 patients with AIH, 74 patients with PBC, and 214 controls. VDR polymorphisms were assessed by BsmI, TaqI, ApaI, and Fok endonuclease digestion after specific polymerase chain reaction (PCR) amplification. We found a significant association between the BsmI polymorphisms in PBC patients in comparison with controls ( 2 ‫؍‬ 9.49, P ‫؍‬ .009). Furthermore we detected a significant association of the Fok polymorphims in AIH patients in comparison to controls ( 2 ‫؍‬ 9.71, P ‫؍‬ .008) indicating a genetic link of VDR polymorphisms to autoimmune liver diseases such as PBC and AIH in German patients. These findings contribute to the knowledge of the complex events determining immunologic tolerance in the liver. Further studies are needed to elucidate the mechanisms by which the vitamin D receptor contributes to the development of autoimmune diseases. (HEPATOLOGY 2002;35:126-131.) A utoimmune hepatitis (AIH) is an immune-mediated chronic inflammation of the liver of unknown etiology, which is characterized by elevated serum transaminase levels, hypergammaglobulinemia, serum autoantibodies, histologic signs of interface hepatitis, and a response to immunosuppressive treatment. 1,2 Genetic factors appear to be involved in the pathogenesis of AIH. However, a conclusive role of a single genetic locus capable of explaining the etiology of AIH has not been identified thus far, and the genetic background of AIH is therefore considered to be polygenic. In previous studies human leukocyte antigens (HLA) DRB1*0301and DRB*0401 have been identified as independent determinants of susceptibility to AIH. 3,4 In addition, tumor necrosis factor ␣ (TNF-␣) and complement C4 alleles have been associated with AIH, despite the observation that both genes exhibit a strong linkage disequilibrium with the HLA A1-B8-DR3 haplotype. [5][6][7] Polymorphisms of the cytotoxic T-lymphocyte antigen 4 (CTLA4*2) have been identified as non-major histocompatibility complex (MHC) susceptibility determinants in AIH type 1. 8 In a recent analysis we have shown a lack of genetic association between idiopathic autoimmune liver diseases and hepatitis as part of the autoimmune polyendocrine syndrome type 1, which is caused by mutations in the autoimmune regulator (AIRE) gene. 9 In primary biliary cirrhosis (PBC) similar genetic factors have been analyzed to elucidate genetic susceptibility. The genetic typing of HLA class II and III alleles revealed a highly significant increase of HLA DRw8 and C4A-Q0 alleles in patients with PBC compared with controls. 10

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“…[220][221][222] Vitamin D has important immunomodulatory properties 223 and depletion or relative resistance may play a part in the aetiology of both T1DM and T2DM, possibly through effects on insulin secretion. 224 It has been shown that allelic variations in the vitamin D receptor (VDR) gene is a significant determinant of the amount of VDR mRNA and VDR protein expressed, 225 and may also affect plasma concentrations of 1,25(OH) 2 D 3 , and the response to oral vitamin D. 226 An association between VDR polymorphisms and T1DM has been reported in South Indian, German and Taiwanese populations, [227][228][229] although not necessarily with the same VDR polymorphisms.…”

Section: Iddm2-the Insulin Gene (Ins) Regionmentioning

confidence: 99%

Genetics of type 1 diabetes mellitus

2002

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Allelic variation in the vitamin D receptor influences susceptibility to IDDM in Indian Asians

Cited by 155 publications

References 36 publications

Maternal intake of vitamin D during pregnancy and risk of advanced beta cell autoimmunity and type 1 diabetes in offspring

Maternal intake of vitamin D during pregnancy and risk of advanced beta cell autoimmunity and type 1 diabetes in offspring

Genetic association of vitamin D receptor polymorphisms with primary biliary cirrhosis and autoimmune hepatitis

Genetics of type 1 diabetes mellitus

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