Cited by 279Vitamin D Research StudiesDiabetes and associated disordersGenetic Associations and Epidemiology

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

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Cooper, Jason D., Smyth, Deborah J., Walker, Neil M., Stevens, Helen, Burren, Oliver S., Wallace, Chris, Greissl, Christopher, Ramos-Lopez, Elizabeth, Hyppönen, Elina, Dunger, David B., Spector, Timothy D., Ouwehand, Willem H., Wang, Thomas J., Badenhoop, Klaus, Todd, John A.·2011·Diabetes

DOI 10.2337/db10-1656PMC PMC3292339

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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.

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Authors: Cooper, J. D., Smyth, D. J., Walker, N. M., Stevens, H., Burren, O. S., Wallace, C., Greissl, C., Ramos-Lopez, E., Hyppönen, E., Dunger, D. B., Spector, T. D., Ouwehand, W. H., Wang, T. J., Badenhoop, K., & Todd, J. A.
Affiliations: University of Cambridge (GB)
University Hospital Frankfurt (DE)
Department of Internal Medicine I, Division of Endocrinology, Diabetes, and Metabolism, University Hospital Frankfurt, Frankfurt am Main, Germany
University College London (GB)
Department of Twin Research and Genetic Epidemiology, King's College London, London, U.K.
National Health Service (GB)
Harvard University (US)
Corresponding author: Todd, John A.
ORCID: Cooper, Jason D.
Smyth, Deborah J.
Walker, Neil M.
Burren, Oliver S.
Wallace, Chris
Hyppönen, Elina
Dunger, David B.
Ouwehand, Willem H.
Wang, Thomas J.
Todd, John A.
Venue: Diabetes
Publisher: American Diabetes Association
Published: 2011-04-23
Volume: 60
Issue: 5
Pages: 1624-1631
ISSN: 0012-1797 (ISSN-L)
1939-327X
DOI: 10.2337/db10-1656
PMC: PMC3292339
OpenAlex: W2155640444
Cited by: 279
References: 50
Citations by year: 2026: 4 · 2025: 4 · 2024: 2 · 2023: 11 · 2022: 12 · 2021: 14 · 2020: 19 · 2019: 23 · 2018: 19 · 2017: 22 · 2016: 23 · 2015: 20 · 2014: 23 · 2013: 37 · 2012: 34
FWCI: 23.63
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-nd
creativecommons.org/licenses/by-nc-nd/3.0/ (vor, 3782 d)
Locations: Diabetes (publishedVersion, cc-by-nc-nd)
PubMed Central (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
UCL Discovery (University College London) (submittedVersion)
Research Portal (King's College London) (submittedVersion)
Funders: Juvenile Diabetes Research Foundation International (068545/Z/02)
American Heart Association
Wellcome Trust (068545/Z/02), 091157, G0000934, 061858, 089989, 068545, 079895, 076113, 076113/C/04/Z)
National Institute for Health and Care Research (PHCS/C4/4/016, NF-SI-0508-10274, NF-SI-0508-10275)
Food Standards Agency
University College London
European Commission (241447, FP7-NAIMIT, 201167)
Queen's University Belfast
Queen's University
Universitetet i Oslo
National Institutes of Health (G0000934, 068545/Z/02, 079895)
Medical Research Council (G0601653, 068545/Z/02, G0000934)
Cambridge Institute for Medical Research, University of Cambridge (079895)
Norwegian Institute of Public Health
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Vitamin D Research Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords: type 1 diabetes, vitamin D deficiency, 25-hydroxyvitamin D, vitamin D metabolism genes, genetic susceptibility, DHCR7, CYP2R1, CYP24A1, CYP27B1, GC, seasonal variation, autoimmune disease susceptibility
MeSH terms: Cytochrome P450 Family 2, Adolescent, Adult, Aged, Child, Child, Preschool, Diabetes Mellitus, Type 1, Genotype, Humans, Middle Aged, Mutation, Steroid Hydroxylases, Vitamin D, 25-Hydroxyvitamin D3 1-alpha-Hydroxylase, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Oxidoreductases Acting on CH-CH Group Donors, Cholestanetriol 26-Monooxygenase, Young Adult, Vitamin D3 24-Hydroxylase

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

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