Abstract
OBJECTIVE: Epidemiological studies have linked vitamin D deficiency with the susceptibility to type 1 diabetes. Higher levels of the active metabolite 1 alpha,25-dihydroxyvitamin D (1 alpha,25(OH)(2)D) could protect from immune destruction of the pancreatic beta-cells. 1 alpha,25(OH)(2)D is derived from its precursor 25-hydroxyvitamin D by the enzyme 1 alpha-hydroxylase encoded by the CYP27B1 gene and is inactivated by 24-hydroxylase encoded by the CYP24A1 gene. Our aim was to study the association between the CYP27B1 and CYP24A1 gene polymorphisms and type 1 diabetes.
RESEARCH DESIGN AND METHODS: We studied 7,854 patients with type 1 diabetes, 8,758 control subjects from the U.K., and 2,774 affected families. We studied four CYP27B1 variants, including common polymorphisms -1260C>A (rs10877012) and +2838T>C (rs4646536) and 16 tag polymorphisms in the CYP24A1 gene.
RESULTS: We found evidence of association with type 1 diabetes for CYP27B1 -1260 and +2838 polymorphisms, which are in perfect linkage disequilibrium. The common C allele of CYP27B1 -1260 was associated with an increased disease risk in the case-control analysis (odds ratio for the C/C genotype 1.22, P = 9.6 x 10(-4)) and in the fully independent collection of families (relative risk for the C/C genotype 1.33, P = 3.9 x 10(-3)). The combined P value for an association with type 1 diabetes was 3.8 x 10(-6). For the CYP24A1 gene, we found no evidence of association with type 1 diabetes (multilocus test, P = 0.23).
CONCLUSIONS: The present data provide evidence that common inherited variation in the vitamin D metabolism affects susceptibility to type 1 diabetes.
Original language | English |
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Pages (from-to) | 2616-21 |
Number of pages | 6 |
Journal | Diabetes |
Volume | 56 |
Issue number | 10 |
DOIs | |
Publication status | Published - Oct 2007 |
Externally published | Yes |
Keywords
- 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/genetics
- Case-Control Studies
- Diabetes Mellitus, Type 1/genetics
- Female
- Genetic Predisposition to Disease
- Genetic Variation
- Genotype
- Humans
- Male
- Nuclear Family
- Polymorphism, Genetic
- Reference Values
- Vitamin D Deficiency/genetics