Type 1 diabetes, genes and vitamin D

two abstracts on this page

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Hypothesis – Three genes show why type 1 diabetes patients need more vitamin D – Mar 2011

Inherited Variation in Vitamin D Genes Is Associated With Predisposition to Autoimmune Disease Type 1 Diabetes.

Diabetes. 2011 Mar 25.
Cooper JD, Smyth DJ, Walker NM, Stevens H, Burren OS, Wallace C, Greissl C, Ramos-Lopez E, Hypponen E, Dunger DB, Spector TD, Ouwehand WH, Wang TJ, Badenhoop K, Todd JA. john.todd@cimr.cam.ac.uk
Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Addenbrooke's Hospital, Cambridge, U.K.

OBJECTIVE Vitamin D deficiency [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.

PMID: 21441443
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Type 1 Diabetes associated with vitamin D only for Asian genes – meta-analysis Feb 2012

Polymorphisms in the vitamin D receptor gene and type 1 diabetes mellitus risk: An update by meta-analysis.

Mol Cell Endocrinol. 2012 Feb 14.
Zhang J, Li W, Liu J, Wu W, Ouyang H, Zhang Q, Wang Y, Liu L, Yang R, Liu X, Meng Q, Lu J.
Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical College, Wenzhou, Zhejiang 325035, China.

Four well known polymorphisms (BsmI, FokI, ApaI, TaqI) in the VDR gene have been implicated in susceptibility to type 1 diabetes mellitus (T1DM), but the results to date have been inconclusive.

The aim of this study was to investigate the association between polymorphisms in the VDR gene and T1DM risk by meta-analysis.

A total of 57 case-control studies in 26 published studies were included. The results indicated that the BsmI polymorphism is associated with increased risk of T1DM (BB+Bb vs. bb: OR=1.30, 95% CI=1.03-1.63), while the FokI, ApaI and TaqI polymorphisms were not. In the subgroup analysis by ethnicity, the increased risk of T1DM remained in the Asian subgroup for the BsmI polymorphism; whereas no significant association was found in other populations for other polymorphisms. Results from the current study suggest that the BsmI polymorphism is associated with increased risk of T1DM, especially in Asians. Further studies are needed to confirm our results.