title: The role of cubilin gene polymorphisms and their influence on 25(OH)D3 and 1,25(OH)2D3 plasma levels in type 1 diabetes patients.
abstract: BACKGROUND
  Megalin and cubilin bind and internalize the 25(OH)D3-DBP complex in the kidney. Once the complex is internalized, 25(OH)D3 is released and activated to 1,25(OH)2D3 the ligand for the vitamin D receptor (VDR). Supporting the important role of cubilin in this process recent findings showed that cubilin deficiency results in decrease of 25(OH)D3 and 1,25(OH)2D3 plasma levels.
  
  
  METHODS
  Two hundred T1D patients and healthy controls (n=200) were genotyped for five polymorphisms (rs3740168, rs3740165, rs1801233, rs1801229 and rs2796835) within the cubilin gene. The polymorphisms were analyzed by RFLP or real time PCR. Statistic analyses were performed by using allele-wise and genotype-wise chi2 testing by using BiAS software. A p-value<0.05 was considered as significant.
  
  
  RESULTS
  We found that the genotype "AA" of the rs3740165 was more frequent in T1D patients compared to healthy controls (26.7% vs. 5.1%, p=4x10(-7)). Nevertheless no association between the rs3740165 polymorphism and the 25(OH)D3 or 1,25(OH)2D3 plasma levels was found. No association with the other studied polymorphisms was observed.
  
  
  CONCLUSIONS
  Thus our findings reveal a novel association of the cubilin rs3740165 polymorphism with type 1 diabetes. Nevertheless how exactly this polymorphism could increase the risk to develop type 1 diabetes is subject for further investigations.
authors.affiliation: Department of Internal Medicine I, Division of Endocrinology, Diabetes, and Metabolism, University Hospital Frankfurt, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ramos-Lopez
authors.forename: Brita
authors.initials: B
authors.lastname: Lange
authors.forename: Marissa
authors.initials: M
authors.lastname: Penna-Martinez
authors.forename: Patrick
authors.initials: P
authors.lastname: Brück
authors.forename: Karolina
authors.initials: K
authors.lastname: Swiech
authors.forename: Sabrina
authors.initials: S
authors.lastname: Mauf
authors.forename: Heinrich
authors.initials: H
authors.lastname: Kahles
authors.forename: Klaus
authors.initials: K
authors.lastname: Badenhoop
mesh_terms: D002112:Calcifediol / Q000097:blood* / Q000235:genetics*; D002117:Calcitriol / Q000097:blood* / Q000235:genetics*; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D015233:Models, Statistical; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011956:Receptors, Cell Surface / Q000097:blood* / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012306:Risk; D012984:Software
chemical_list: D011956:Receptors, Cell Surface; C029486:intrinsic factor-cobalamin receptor; D002117:Calcitriol; D002112:Calcifediol