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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

Author:
Sentinelli, F., Bertoccini, L., Barchetta, I., Capoccia, D., Incani, M., Pani, M.G., Loche, S., Angelico, F., Arca, M., Morini, S., Manconi, E., Lenzi, A., Cossu, E., Leonetti, F., Baroni, M.G., Cavallo, M.G.
Source:
Nutrition, metabolism, and cardiovascular diseases 2016 v.26 no.5 pp. 407-413
ISSN:
0939-4753
Subject:
adults, autoimmunity, biochemical pathways, calcitriol receptors, cardiovascular diseases, childhood obesity, children, genes, genotyping, glucose, homozygosity, insulin, insulin resistance, insulin secretion, islets of Langerhans, metabolism, neoplasms, noninsulin-dependent diabetes mellitus, vitamin D
Abstract:
1α,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.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 β-cell insulin secretion. In children, the AA genotype was associated with 2 h high-normal glucose, a marker of cardio-metabolic risk.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.
Agid:
6080642