PMID- 27052925
OWN - NLM
STAT- MEDLINE
DCOM- 20170731
LR  - 20181217
IS  - 1590-3729 (Electronic)
IS  - 0939-4753 (Linking)
VI  - 26
IP  - 5
DP  - 2016 May
TI  - The vitamin D receptor (VDR) gene rs11568820 variant is associated with type 2 
      diabetes and impaired insulin secretion in Italian adult subjects, and associates 
      with increased cardio-metabolic risk in children.
PG  - 407-13
LID - S0939-4753(15)30260-X [pii]
LID - 10.1016/j.numecd.2016.02.004 [doi]
AB  - BACKGROUND AND AIMS: 1alpha,25-dihydroxyvitamin-D3, the biologically active vitamin 
      D, plays a central role in several metabolic pathways through the binding to the 
      vitamin D receptor (VDR). VDR has been shown to be involved in cardiovascular 
      diseases, cancer, autoimmunity and type 2 diabetes mellitus (T2DM). Several 
      polymorphisms in the VDR gene have been described. Among these, the rs11568820 
      G-to-A nucleotide substitution was found to be functional, modulating the 
      transcription of the VDR gene. Objective of this study was to perform an 
      association study between rs11568820 polymorphism and T2DM in a cohort of Italian 
      adults with T2DM and in non-diabetic controls. To add further insight into the 
      role of VDR gene we explored whether this association begins early in life in 
      overweight/obese children, or becomes manifest only in adulthood. METHODS AND 
      RESULTS: As many as 1788 adults and 878 children were genotyped for the 
      rs11568820 polymorphism. All participants underwent oral glucose tolerance tests 
      (OGTT), with measurement of glucose and insulin levels. Indices of 
      insulin-resistance and secretion were also calculated. The AA genotype was 
      significantly more frequent in adults with T2DM compared to controls (7.5% vs. 
      4.6%, P = 0.037), and conferred a higher risk of T2DM 
      (ORHom = 1.69C.I. = [1.13-2.53], P = 0.011). In the adult cohort, rs11568820 was 
      also associated with reduced indices of beta-cell insulin secretion. In children, 
      the AA genotype was associated with 2 h high-normal glucose, a marker of 
      cardio-metabolic risk. CONCLUSIONS: Our study demonstrates for the first time 
      that VDR gene AA carriers have higher risk of T2DM and impaired insulin 
      secretion. In children, the association between AA homozygous and high-normal 2h 
      glucose suggests that mild alterations associated with this genotype may appear 
      early in life.
CI  - Copyright (c) 2016 The Italian Society of Diabetology, the Italian Society for the 
      Study of Atherosclerosis, the Italian Society of Human Nutrition, and the 
      Department of Clinical Medicine and Surgery, Federico II University. Published by 
      Elsevier B.V. All rights reserved.
FAU - Sentinelli, F
AU  - Sentinelli F
AD  - Department of Experimental Medicine, Sapienza University of Rome, Italy.
FAU - Bertoccini, L
AU  - Bertoccini L
AD  - Department of Experimental Medicine, Sapienza University of Rome, Italy.
FAU - Barchetta, I
AU  - Barchetta I
AD  - Internal Medicine Unit, Department of Internal Medicine and Medical Specialties, 
      Sapienza University of Rome, Italy.
FAU - Capoccia, D
AU  - Capoccia D
AD  - Department of Experimental Medicine, Sapienza University of Rome, Italy.
FAU - Incani, M
AU  - Incani M
AD  - Endocrinology and Diabetes, Department of Medical Sciences, University of 
      Cagliari, Cagliari, Italy.
FAU - Pani, M G
AU  - Pani MG
AD  - Endocrinology and Diabetes, Department of Medical Sciences, University of 
      Cagliari, Cagliari, Italy.
FAU - Loche, S
AU  - Loche S
AD  - Pediatric Endocrine Unit, Regional Hospital for Microcitemia, Cagliari, Italy.
FAU - Angelico, F
AU  - Angelico F
AD  - Internal Medicine Unit, Department of Internal Medicine and Medical Specialties, 
      Sapienza University of Rome, Italy.
FAU - Arca, M
AU  - Arca M
AD  - Internal Medicine Unit, Department of Internal Medicine and Medical Specialties, 
      Sapienza University of Rome, Italy.
FAU - Morini, S
AU  - Morini S
AD  - Human Anatomy, (CIR), University Campus Bio-Medico, Rome, Italy.
FAU - Manconi, E
AU  - Manconi E
AD  - Endocrinology and Diabetes, Department of Medical Sciences, University of 
      Cagliari, Cagliari, Italy.
FAU - Lenzi, A
AU  - Lenzi A
AD  - Department of Experimental Medicine, Sapienza University of Rome, Italy.
FAU - Cossu, E
AU  - Cossu E
AD  - Endocrinology and Diabetes, Department of Medical Sciences, University of 
      Cagliari, Cagliari, Italy.
FAU - Leonetti, F
AU  - Leonetti F
AD  - Department of Experimental Medicine, Sapienza University of Rome, Italy.
FAU - Baroni, M G
AU  - Baroni MG
AD  - Department of Experimental Medicine, Sapienza University of Rome, Italy; 
      Endocrinology and Diabetes, Department of Medical Sciences, University of 
      Cagliari, Cagliari, Italy. Electronic address: marco.baroni@uniroma1.it.
FAU - Cavallo, M G
AU  - Cavallo MG
AD  - Internal Medicine Unit, Department of Internal Medicine and Medical Specialties, 
      Sapienza University of Rome, Italy.
LA  - eng
PT  - Journal Article
DEP - 20160219
PL  - Netherlands
TA  - Nutr Metab Cardiovasc Dis
JT  - Nutrition, metabolism, and cardiovascular diseases : NMCD
JID - 9111474
RN  - 0 (Biomarkers)
RN  - 0 (Blood Glucose)
RN  - 0 (Insulin)
RN  - 0 (Receptors, Calcitriol)
RN  - 0 (VDR protein, human)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Age of Onset
MH  - Biomarkers/blood
MH  - Blood Glucose/*metabolism
MH  - Case-Control Studies
MH  - Chi-Square Distribution
MH  - Child
MH  - Cross-Sectional Studies
MH  - Diabetes Mellitus, Type 2/blood/diagnosis/*genetics
MH  - Female
MH  - Gene Frequency
MH  - Genetic Association Studies
MH  - Genetic Predisposition to Disease
MH  - Glucose Tolerance Test
MH  - Heterozygote
MH  - Homozygote
MH  - Humans
MH  - Insulin/*blood/metabolism
MH  - Insulin Resistance/genetics
MH  - Insulin Secretion
MH  - Italy
MH  - Linear Models
MH  - Logistic Models
MH  - Male
MH  - Metabolic Syndrome/blood/diagnosis/*genetics
MH  - Middle Aged
MH  - Odds Ratio
MH  - Pediatric Obesity/blood/diagnosis/*genetics
MH  - Phenotype
MH  - *Polymorphism, Single Nucleotide
MH  - Receptors, Calcitriol/*genetics/metabolism
MH  - Risk Factors
OTO - NOTNLM
OT  - Insulin secretion
OT  - Insulin sensitivity
OT  - SNP
OT  - VDR gene
EDAT- 2016/04/08 06:00
MHDA- 2017/08/02 06:00
CRDT- 2016/04/08 06:00
PHST- 2015/10/09 00:00 [received]
PHST- 2015/12/30 00:00 [revised]
PHST- 2016/02/01 00:00 [accepted]
PHST- 2016/04/08 06:00 [entrez]
PHST- 2016/04/08 06:00 [pubmed]
PHST- 2017/08/02 06:00 [medline]
AID - S0939-4753(15)30260-X [pii]
AID - 10.1016/j.numecd.2016.02.004 [doi]
PST - ppublish
SO  - Nutr Metab Cardiovasc Dis. 2016 May;26(5):407-13. doi: 
      10.1016/j.numecd.2016.02.004. Epub 2016 Feb 19.