Inherited Variation in Vitamin D Genes Is Associated With Predisposition to Autoimmune Disease Type 1 Diabetes
| العنوان: | Inherited Variation in Vitamin D Genes Is Associated With Predisposition to Autoimmune Disease Type 1 Diabetes |
|---|---|
| المؤلفون: | Willem H. Ouwehand, Elizabeth Ramos-Lopez, Chris Wallace, Thomas J. Wang, Neil Walker, Helen Stevens, Tim D. Spector, David B. Dunger, John A. Todd, Deborah J. Smyth, Jason D. Cooper, Christopher Greissl, Oliver S. Burren, Klaus Badenhoop, Elina Hyppönen |
| المساهمون: | Cooper, Jason D, Smyth, Deborah J, Walker, Neil M, Stevens, Helen, Burren, Oliver S, Wallace, Chris, Greissl, Christopher, Ramos-Lopez, Elizabeth, Hypponen, Elina Tuulikki, Dunger, David B, Spector, Timothy D, Ouwehand, Willem H, Wang, Thomas J, Badenboop, Klaus, Todd, John A |
| المصدر: | Diabetes Diabetes; Vol 60 |
| بيانات النشر: | American Diabetes Association, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Endocrinology, Diabetes and Metabolism, Vitamin D3 24-Hydroxylase, 0302 clinical medicine, adolescents, Vitamin D, Child, 0303 health sciences, education.field_of_study, Middle Aged, Micronutrient, 3. Good health, Type 1 diabetes, Child, Preschool, Cholestanetriol 26-Monooxygenase, Adult, medicine.medical_specialty, Oxidoreductases Acting on CH-CH Group Donors, Adolescent, Genotype, vitamin D deficiency, Population, 030209 endocrinology & metabolism, Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, 03 medical and health sciences, Young Adult, children, CYP24A1, Internal medicine, Internal Medicine, Vitamin D and neurology, medicine, Genetics, Humans, Genetic Predisposition to Disease, education, Cytochrome P450 Family 2, 030304 developmental biology, Aged, 25-Hydroxyvitamin D3 1-alpha-Hydroxylase, business.industry, medicine.disease, Endocrinology, Diabetes Mellitus, Type 1, Mutation, Steroid Hydroxylases, business |
| الوصف: | OBJECTIVE Vitamin D deficiency (25-hydroxyvitamin D [25(OH)D] 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. |
| اللغة: | English |
| تدمد: | 1939-327X 0012-1797 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9bd842575f278341e8f9e00f34b54b05Test http://europepmc.org/articles/PMC3292339Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9bd842575f278341e8f9e00f34b54b05 |
| قاعدة البيانات: | OpenAIRE |
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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. 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