CACNA1E variants affect beta cell function in patients with newly diagnosed type 2 diabetes. the Verona newly diagnosed type 2 diabetes study (VNDS) 3.

<h4>Background</h4>Genetic variability of the major subunit (CACNA1E) of the voltage-dependent Ca(2+) channel Ca(V)2.3 is associated to risk of type 2 diabetes, insulin resistance and impaired insulin secretion in nondiabetic subjects. The aim of the study was to test whether CACNA1E com...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Maddalena Trombetta, Sara Bonetti, Marialinda Boselli, Fabiola Turrini, Giovanni Malerba, Elisabetta Trabetti, PierFranco Pignatti, Enzo Bonora, Riccardo C Bonadonna
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/98635ed78a904f5a8ffdb8b10ccb9365
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:98635ed78a904f5a8ffdb8b10ccb9365
record_format	dspace
spelling	oai:doaj.org-article:98635ed78a904f5a8ffdb8b10ccb93652021-11-18T07:25:38ZCACNA1E variants affect beta cell function in patients with newly diagnosed type 2 diabetes. the Verona newly diagnosed type 2 diabetes study (VNDS) 3.1932-620310.1371/journal.pone.0032755https://doaj.org/article/98635ed78a904f5a8ffdb8b10ccb93652012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22427875/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Genetic variability of the major subunit (CACNA1E) of the voltage-dependent Ca(2+) channel Ca(V)2.3 is associated to risk of type 2 diabetes, insulin resistance and impaired insulin secretion in nondiabetic subjects. The aim of the study was to test whether CACNA1E common variability affects beta cell function and/or insulin sensitivity in patients with newly diagnosed type 2 diabetes.<h4>Methodology/principal findings</h4>In 595 GAD-negative, drug naïve patients (mean ± SD; age: 58.5 ± 10.2 yrs; BMI: 29.9 ± 5 kg/m(2), HbA1c: 7.0±1.3) with newly diagnosed type 2 diabetes we: 1. genotyped 10 tag SNPs in CACNA1E region reportedly covering ∼93% of CACNA1E common variability: rs558994, rs679931, rs2184945, rs10797728, rs3905011, rs12071300, rs175338, rs3753737, rs2253388 and rs4652679; 2. assessed clinical phenotypes, insulin sensitivity by the euglycemic insulin clamp and beta cell function by state-of-art modelling of glucose/C-peptide curves during OGTT. Five CACNA1E tag SNPs (rs10797728, rs175338, rs2184945, rs3905011 and rs4652679) were associated with specific aspects of beta cell function (p<0.05-0.01). Both major alleles of rs2184945 and rs3905011 were each (p<0.01 and p<0.005, respectively) associated to reduced proportional control with a demonstrable additive effect (p<0.005). In contrast, only the major allele of rs2253388 was related weakly to more severe insulin resistance (p<0.05).<h4>Conclusions/significance</h4>In patients with newly diagnosed type 2 diabetes CACNA1E common variability is strongly associated to beta cell function. Genotyping CACNA1E might be of help to infer the beta cell functional phenotype and to select a personalized treatment.Maddalena TrombettaSara BonettiMarialinda BoselliFabiola TurriniGiovanni MalerbaElisabetta TrabettiPierFranco PignattiEnzo BonoraRiccardo C BonadonnaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 3, p e32755 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Maddalena Trombetta Sara Bonetti Marialinda Boselli Fabiola Turrini Giovanni Malerba Elisabetta Trabetti PierFranco Pignatti Enzo Bonora Riccardo C Bonadonna CACNA1E variants affect beta cell function in patients with newly diagnosed type 2 diabetes. the Verona newly diagnosed type 2 diabetes study (VNDS) 3.
description	<h4>Background</h4>Genetic variability of the major subunit (CACNA1E) of the voltage-dependent Ca(2+) channel Ca(V)2.3 is associated to risk of type 2 diabetes, insulin resistance and impaired insulin secretion in nondiabetic subjects. The aim of the study was to test whether CACNA1E common variability affects beta cell function and/or insulin sensitivity in patients with newly diagnosed type 2 diabetes.<h4>Methodology/principal findings</h4>In 595 GAD-negative, drug naïve patients (mean ± SD; age: 58.5 ± 10.2 yrs; BMI: 29.9 ± 5 kg/m(2), HbA1c: 7.0±1.3) with newly diagnosed type 2 diabetes we: 1. genotyped 10 tag SNPs in CACNA1E region reportedly covering ∼93% of CACNA1E common variability: rs558994, rs679931, rs2184945, rs10797728, rs3905011, rs12071300, rs175338, rs3753737, rs2253388 and rs4652679; 2. assessed clinical phenotypes, insulin sensitivity by the euglycemic insulin clamp and beta cell function by state-of-art modelling of glucose/C-peptide curves during OGTT. Five CACNA1E tag SNPs (rs10797728, rs175338, rs2184945, rs3905011 and rs4652679) were associated with specific aspects of beta cell function (p<0.05-0.01). Both major alleles of rs2184945 and rs3905011 were each (p<0.01 and p<0.005, respectively) associated to reduced proportional control with a demonstrable additive effect (p<0.005). In contrast, only the major allele of rs2253388 was related weakly to more severe insulin resistance (p<0.05).<h4>Conclusions/significance</h4>In patients with newly diagnosed type 2 diabetes CACNA1E common variability is strongly associated to beta cell function. Genotyping CACNA1E might be of help to infer the beta cell functional phenotype and to select a personalized treatment.
format	article
author	Maddalena Trombetta Sara Bonetti Marialinda Boselli Fabiola Turrini Giovanni Malerba Elisabetta Trabetti PierFranco Pignatti Enzo Bonora Riccardo C Bonadonna
author_facet	Maddalena Trombetta Sara Bonetti Marialinda Boselli Fabiola Turrini Giovanni Malerba Elisabetta Trabetti PierFranco Pignatti Enzo Bonora Riccardo C Bonadonna
author_sort	Maddalena Trombetta
title	CACNA1E variants affect beta cell function in patients with newly diagnosed type 2 diabetes. the Verona newly diagnosed type 2 diabetes study (VNDS) 3.
title_short	CACNA1E variants affect beta cell function in patients with newly diagnosed type 2 diabetes. the Verona newly diagnosed type 2 diabetes study (VNDS) 3.
title_full	CACNA1E variants affect beta cell function in patients with newly diagnosed type 2 diabetes. the Verona newly diagnosed type 2 diabetes study (VNDS) 3.
title_fullStr	CACNA1E variants affect beta cell function in patients with newly diagnosed type 2 diabetes. the Verona newly diagnosed type 2 diabetes study (VNDS) 3.
title_full_unstemmed	CACNA1E variants affect beta cell function in patients with newly diagnosed type 2 diabetes. the Verona newly diagnosed type 2 diabetes study (VNDS) 3.
title_sort	cacna1e variants affect beta cell function in patients with newly diagnosed type 2 diabetes. the verona newly diagnosed type 2 diabetes study (vnds) 3.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/98635ed78a904f5a8ffdb8b10ccb9365
work_keys_str_mv	AT maddalenatrombetta cacna1evariantsaffectbetacellfunctioninpatientswithnewlydiagnosedtype2diabetestheveronanewlydiagnosedtype2diabetesstudyvnds3 AT sarabonetti cacna1evariantsaffectbetacellfunctioninpatientswithnewlydiagnosedtype2diabetestheveronanewlydiagnosedtype2diabetesstudyvnds3 AT marialindaboselli cacna1evariantsaffectbetacellfunctioninpatientswithnewlydiagnosedtype2diabetestheveronanewlydiagnosedtype2diabetesstudyvnds3 AT fabiolaturrini cacna1evariantsaffectbetacellfunctioninpatientswithnewlydiagnosedtype2diabetestheveronanewlydiagnosedtype2diabetesstudyvnds3 AT giovannimalerba cacna1evariantsaffectbetacellfunctioninpatientswithnewlydiagnosedtype2diabetestheveronanewlydiagnosedtype2diabetesstudyvnds3 AT elisabettatrabetti cacna1evariantsaffectbetacellfunctioninpatientswithnewlydiagnosedtype2diabetestheveronanewlydiagnosedtype2diabetesstudyvnds3 AT pierfrancopignatti cacna1evariantsaffectbetacellfunctioninpatientswithnewlydiagnosedtype2diabetestheveronanewlydiagnosedtype2diabetesstudyvnds3 AT enzobonora cacna1evariantsaffectbetacellfunctioninpatientswithnewlydiagnosedtype2diabetestheveronanewlydiagnosedtype2diabetesstudyvnds3 AT riccardocbonadonna cacna1evariantsaffectbetacellfunctioninpatientswithnewlydiagnosedtype2diabetestheveronanewlydiagnosedtype2diabetesstudyvnds3
_version_	1718423489687322624

CACNA1E variants affect beta cell function in patients with newly diagnosed type 2 diabetes. the Verona newly diagnosed type 2 diabetes study (VNDS) 3.

Ejemplares similares