Inherited Variation in Vitamin D Genes Is Associated With Predisposition to Autoimmune Disease Type 1 Diabetes
Year: 2011
Type: article
Study design: Observational Study
Abstract: OBJECTIVE: Vitamin D deficiency (25-hydroxyvitamin D [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.
Source: Diabetes
DOI: 10.2337/db10-1656
Institutions: University of Cambridge, Breakthrough T1D UK, Addenbrooke's Hospital, Wellcome Trust, University Hospital Frankfurt, University College London, Medical Research Council, King's College London, National Health Service, Wellcome Sanger Institute, Harvard University, Massachusetts General Hospital, Framingham Heart Study
Language: English
Topic: Vitamin D Research Studies
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funders: Juvenile Diabetes Research Foundation International, American Heart Association, Wellcome Trust, National Institute for Health and Care Research, Food Standards Agency, University College London, European Commission, Queen's University Belfast, Queen's University, Universitetet i Oslo, National Institutes of Health, Medical Research Council, Cambridge Institute for Medical Research, University of Cambridge, Norwegian Institute of Public Health
Awards: G1137313802, Novel immunotherapies for type 1 diabetes, G1700490681, Pathophysiology and natural course of autoimmune adrenal failure in Europe, Diabetes and Inflammation Laboratory., G2824707892, G3349769430, G3511822935, JDRF/WT Diabetes and Inflammation Laboratory., G3860752689, Genes and Pathways in Type 1 Diabetes., NIHR Senior Investigator Award, NIHR Senior Investigator Award, G5502349062, G5568298347, A national DNA control series for genetic case-control studies based on the British 1958 birth cohort, G6661414329, G67356480, Cambridge Institute for Medical Research (CIMR)., G744684802, G8900108227, The genetics of weight, BMI, adiposity and obesity, Design and implementation of large-scale genetic association studies of commondiseases.
OpenAlex ID: W2155640444