title: The vitamin D receptor functional variant rs2228570 (C>T) does not associate with type 2 diabetes mellitus.
abstract: OBJECTIVE
  Vitamin D acts through the binding to the vitamin D receptor (VDR). Several polymorphisms in VDR gene have been studied. Among these, the rs2228570 C>T (FokI) variant has been demonstrated to be functional, leading to a protein with a different size and activity. So far, genetic studies on the association between VDR gene rs2228570 single nucleotide polymorphism (SNP) and type 2 diabetes mellitus (T2DM) showed contradictory results. Thus, we performed an association study in a large cohort of adult Italian subjects with T2DM and in nondiabetic controls.
  
  
  METHODS
  For this study, 1713 subjects, 883 T2DM patients and 830 controls, were genotyped for the polymorphism. All participants without a diagnosis of diabetes underwent oral glucose tolerance test (OGTT), with measurement of glucose and insulin levels. Indices of insulin resistance (Homeostatic model assessment of insulin resistance, insulin sensitivity index), secretion (homeostatic model assessment for beta-cell, corrected insulin response at 30 minutes) and disposition index were calculated.
  
  
  RESULTS
  Genotype distributions and allele frequencies did not show difference between T2DM subjects and controls. We did not find significant differences among the three genotypes regarding gender, age, BMI, waist, hip, waist-to-hip ratio, and blood pressure. There were also no significant differences in lipid parameters, aspartate aminotransferase, and alanine aminotransferase levels. We tested for association with OGTT-derived data and surrogate indices of insulin resistance and secretion. We did not find significant differences among the genotypes in any of above-mentioned parameters. Furthermore, vitamin D levels were measured in a subgroup of subjects. We did not find significant differences among the genotypes.
  
  
  CONCLUSIONS
  Our study does not provide evidence for the association of the rs2228570 polymorphism with T2DM in a Caucasian population.
authors.affiliation: a Department of Experimental Medicine , Sapienza University of Rome , Rome , Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Bertoccini
authors.affiliation: a Department of Experimental Medicine , Sapienza University of Rome , Rome , Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Sentinelli
authors.affiliation: a Department of Experimental Medicine , Sapienza University of Rome , Rome , Italy.
authors.forename: Frida
authors.initials: F
authors.lastname: Leonetti
authors.affiliation: a Department of Experimental Medicine , Sapienza University of Rome , Rome , Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Bailetti
authors.affiliation: a Department of Experimental Medicine , Sapienza University of Rome , Rome , Italy.
authors.forename: Danila
authors.initials: D
authors.lastname: Capoccia
authors.affiliation: b Internal Medicine Unit, Department of Internal Medicine and Medical Specialties , Sapienza University of Rome , Rome , Italy.
authors.forename: Flavia A
authors.initials: FA
authors.lastname: Cimini
authors.affiliation: b Internal Medicine Unit, Department of Internal Medicine and Medical Specialties , Sapienza University of Rome , Rome , Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Barchetta
authors.affiliation: c Endocrinology and Diabetes, Department of Medical Sciences , University of Cagliari , Cagliari , Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Incani
authors.affiliation: a Department of Experimental Medicine , Sapienza University of Rome , Rome , Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Lenzi
authors.affiliation: c Endocrinology and Diabetes, Department of Medical Sciences , University of Cagliari , Cagliari , Italy.
authors.forename: Efisio
authors.initials: E
authors.lastname: Cossu
authors.affiliation: b Internal Medicine Unit, Department of Internal Medicine and Medical Specialties , Sapienza University of Rome , Rome , Italy.
authors.forename: M Gisella
authors.initials: MG
authors.lastname: Cavallo
authors.affiliation: a Department of Experimental Medicine , Sapienza University of Rome , Rome , Italy.|d IRCCS Neuromed , Pozzilli.
authors.forename: Marco G
authors.identifier: http://orcid.org/0000-0002-3224-6078
authors.initials: MG
authors.lastname: Baroni
mesh_terms: D015652:25-Hydroxyvitamin D 2 / Q000097:blood; D000328:Adult; D002112:Calcifediol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007558:Italy; D008297:Male; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism; D015203:Reproducibility of Results
chemical_list: D018167:Receptors, Calcitriol; C579457:VDR protein, human; D015652:25-Hydroxyvitamin D 2; D002112:Calcifediol
keywords: SNP; VDR gene; type 2 diabetes; vitamin D