CYP27B1 polymorphisms variants are associated with type 1 diabetes mellitus in Germans

López, Ernesto; Regulla, Karoline; Pani, Michael A.; Krause, Maren; Usadel, K. H.; Badenhoop, Klaus

doi:10.1016/j.jsbmb.2004.03.095

Cited by 41 publications

(36 citation statements)

References 22 publications

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“…2). Indeed, 1a-hydroxylation might be impaired by the HIV infection itself [22] as well as through polymorphisms in 1a-hydroxylase (CYP27B1) [23,24] or PIs [25].Remarkably, although all our patients had vitamin D deficiency, BMD was relatively normal, and only a low prevalence of osteopenia (32%) and no osteoporosis in the femoral neck was observed. In elderly and younger women with a poor vitamin D status, a positive correlation of vitamin D levels with BMD of the proximal femur and vertebrae has been reported [3,20].…”

mentioning

confidence: 69%

“…There were no significant differences in the median circulating IL-6 plasma levels of these patients after 24 …”

Section: Effects Of Cholecalciferol On Inflammatory Markersmentioning

confidence: 82%

“…2). Indeed, 1a-hydroxylation might be impaired by the HIV infection itself [22] as well as through polymorphisms in 1a-hydroxylase (CYP27B1) [23,24] or PIs [25].…”

Section: Discussionmentioning

confidence: 99%

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The effect of cholecalciferol supplementation on vitamin D levels and insulin sensitivity is dose related in vitamin D‐deficient HIV‐1‐infected patients

et al. 2008

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ObjectiveThe aim of this study was to explore the effects of cholecalciferol supplementation on vitamin D levels, bone mineral density (BMD), body fat distribution and insulin sensitivity in vitamin D-deficient HIV-1-infected patients. MethodsTwenty vitamin D-deficient HIV-1-infected patients were prospectively treated with 2000 IU cholecalciferol/day for 14 weeks, whereafter treatment was continued with half this dosage until 48 weeks. BMD, body fat distribution, 1,25-dihydroxy vitamin D 3 (1,25(OH) 2 D 3 ), fasting glucose, insulin, adiponectin, leptin, interleukin (IL)-6 and tumour necrosis factor (TNF)-a were measured at baseline, and at 24 and 48 weeks. Parathyroid hormone (PTH), 25-hydroxy vitamin D 3 [25(OH)D 3 ], cholesterol and triglycerides were measured at baseline, and at 12, 24 and 48 weeks. ResultsAfter 24 weeks, cholecalciferol supplementation significantly increased 25(OH)D 3 and 1,25(OH) 2 D 3 levels and decreased PTH and insulin sensitivity. After 48 weeks, however, only 25(OH)D 3 levels remained significantly different from baseline, while the other parameter levels returned to baseline, suggesting a dose-response effect. Cholecalciferol had no effect on BMD, adipokines and triglycerides. ConclusionsThe effect of cholecalciferol treatment in this cohort appears to be dose dependent. Cholecalciferol dosages of !2000 IU are necessary to achieve 1,25(OH) 2 D 3 levels that significantly decrease PTH, but also negatively affect insulin sensitivity. The results of this hypothesis-driven explorative study need to be confirmed in larger clinical trials.Keywords: bone mineral density, cholecalciferol supplementation, HIV/AIDS, insulin sensitivity, vitamin D deficiency Vitamin D is mainly known for its function in regulation of calcium homeostasis and maintenance of bone mineralization. Serum 25(OH)D 3 levels are the best indicator of vitamin D status [3]. The optimal 25(OH)D 3 level needed for maintenance of adequate bone mineral density (BMD) is unknown. A significant positive association between 25(OH)D 3 levels and BMD has been observed in both Another emerging problem associated with the widespread use of HAART is the lipodystrophy syndrome, which is characterized by altered fat distribution (central fat accumulation and peripheral fat loss) and metabolic alterations (dyslipidaemia, insulin resistance and diabetes mellitus). The vitamin D receptor (VDR) has also been found on adipocytes, suggesting a role for vitamin D in fat metabolism [7]. Indeed, it was demonstrated in vitro that 1,25-dihydroxy vitamin D 3 [1,25(OH) 2 D 3 ] inhibits adipocyte differentiation through, among other effects, inhibition of peroxisome proliferator-activated receptor-g (PPAR-g) [7][8][9]. However, 1,25(OH) 2 D 3 can elicit a nongenomic action on adipocytes in vitro, resulting in increased intracellular calcium levels and corresponding stimulation of adipogenesis and inhibition of lipolysis [10].A number of genetic polymorphisms in the VDR gene and low 25(OH)D 3 levels have been associated with insulin resistance and wi...

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mentioning

confidence: 69%

“…There were no significant differences in the median circulating IL-6 plasma levels of these patients after 24 …”

Section: Effects Of Cholecalciferol On Inflammatory Markersmentioning

confidence: 82%

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The effect of cholecalciferol supplementation on vitamin D levels and insulin sensitivity is dose related in vitamin D‐deficient HIV‐1‐infected patients

et al. 2008

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“…Two additional SNPs were included either because of reported association with type 1 diabetes (rs10877012) or because of a proposed involvement in MS susceptibility (rs4646536). 8,10 A complete list of included SNPs is shown in Table 1.…”

Section: Snp Selectionmentioning

confidence: 99%

“…In the combined cohort, rs703842, which lies 1.76 kb upstream of CYP27B1, was associated with MS (P¼5.4Â10 À11 ). 6 Association with CYP27B1 has been seen in autoimmune diseases; rs4646536 (+2838T4C), which is in high linkage disequilibrium (LD) with rs703842, and rs10877012 (À1260C4A) have previously been associated with type 1 diabetes, 7,8 Hashimoto's thyroiditis and Graves' disease. 9 Rs4646536 and rs703842 have been associated with 25-hydroxyvitamin D3 (25(OH)D 3 ) levels in Canadian twins, in which at least one of the twins suffered from MS. 10 Vitamin D3 is naturally produced in the skin after UV B radiation, and can also be supplied in the diet.…”

Section: Introductionmentioning

confidence: 99%

Confirmation of association between multiple sclerosis and CYP27B1

et al. 2010

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Multiple sclerosis, MS (OMIM No. 126200), is a complex inflammatory disease that is characterized by lesions in the central nervous system. Both genes and other environmental factors influence disease susceptibility. One of the environmental factors that has been implicated in MS and autoimmune disease, such as type 1 diabetes, is vitamin D deficiency, in which patients have lower levels of 25-hydroxyvitamin D3 (25-OHD 3 ) in blood than do controls. Previtamin D 3 is produced in the skin, and turned into 25-OHD 3 in the liver. In the kidney, skin and immune cells, 25-OHD 3 is turned into bioactive 1,25(OH) 2 D 3 by the enzyme coded by CYP27B1 (cytochrome P450 family 27 subfamily B peptide 1) on chromosome 12q13.1-3. 1,25(OH) 2 D 3 binds to the vitamin D receptor, expressed in T cells and antigen-presenting cells. 1,25(OH) 2 D 3 has a suppressive role in the adaptive immune system, decreasing T-cell and dendritic cell maturation, proliferation and differentiation, shifting the balance between T-helper 1 (Th1) and Th2 cells in favor of Th2 cells and increasing the suppressive function of regulatory T cells. Rs703842 in the 12q13-14 region was associated with MS in a recent study by the Australian and New Zealand Multiple Sclerosis Genetics Consortium (ANZgene). We show associations with three SNPs in this region in our Swedish materials (2158 cases, 1759 controls) rs4646536, rs10877012 and rs10877015 (P¼0.01, 0.01 and 3.5Â10 À3 , respectively). We imputed rs703842 SNP and performed a joint analysis with the ANZgene results, reaching a significant association for rs703842 (P¼5.1Â10 À11 ; odds ratio 0.83; 95% confidence interval 0.79-0.88). Owing to its close association with 25-OHD 3 , our results lend further support to the role of vitamin D in MS pathology.

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The role of vitamin D in protecting type 1 diabetes mellitus

Lương

Nguyễn

Nguyen

2005

Diabetes Metabolism Res

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The relationship between autoimmune diabetes or type 1 diabetes mellitus and vitamin D has been reported in the literature. Many factors, environmental and genetic, have been known, as risk factors, to cause both type 1 diabetes and vitamin D deficiency. Vitamin D treatment has improved or prevented type 1 diabetes mellitus in animals and humans. Vitamin D also has been known to protect from autoimmune diseases in animal models. Therefore, it would be interesting to review the role of vitamin D in type 1 diabetes mellitus.

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CYP27B1 polymorphisms variants are associated with type 1 diabetes mellitus in Germans

Cited by 41 publications

References 22 publications

The effect of cholecalciferol supplementation on vitamin D levels and insulin sensitivity is dose related in vitamin D‐deficient HIV‐1‐infected patients

The effect of cholecalciferol supplementation on vitamin D levels and insulin sensitivity is dose related in vitamin D‐deficient HIV‐1‐infected patients

Confirmation of association between multiple sclerosis and CYP27B1

The role of vitamin D in protecting type 1 diabetes mellitus

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