title: Association of the vitamin D metabolism gene CYP27B1 with type 1 diabetes.
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.
  
  
  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.
authors.affiliation: Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Bailey
authors.forename: Jason D
authors.initials: JD
authors.lastname: Cooper
authors.forename: Lauren
authors.initials: L
authors.lastname: Zeitels
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Smyth
authors.forename: Jennie H M
authors.initials: JH
authors.lastname: Yang
authors.forename: Neil M
authors.initials: NM
authors.lastname: Walker
authors.forename: Elina
authors.initials: E
authors.lastname: Hyppönen
authors.forename: David B
authors.initials: DB
authors.lastname: Dunger
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ramos-Lopez
authors.forename: Klaus
authors.initials: K
authors.lastname: Badenhoop
authors.forename: Sergey
authors.initials: S
authors.lastname: Nejentsev
authors.forename: John A
authors.initials: JA
authors.lastname: Todd
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics*; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D009679:Nuclear Family; D011110:Polymorphism, Genetic; D012016:Reference Values; D014808:Vitamin D Deficiency / Q000235:genetics
chemical_list: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase