期刊
DIABETES
卷 56, 期 10, 页码 2616-2621出版社
AMER DIABETES ASSOC
DOI: 10.2337/db07-0652
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资金
- MRC [G0000934] Funding Source: UKRI
- Medical Research Council [G0000934] Funding Source: Medline
- Wellcome Trust [061858, 068545/Z/02] Funding Source: Medline
- Department of Health [PHCS/C4/4/016] Funding Source: Medline
- Medical Research Council [G0000934, G0400546B] Funding Source: researchfish
- National Institute for Health Research [PHCS/C4/4/016] Funding Source: researchfish
OBJECTIVE-Epidemiological studies have linked vitamin D deficiency with the susceptibility to type I 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 P-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 CYP24AI 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 I diabetes.
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