Decreased insulin secretion and increased risk of type 2 diabetes associated with allelic variations of the WFS1 gene: the Data from Epidemiological Study on the Insulin Resistance Syndrome (DESIR) prospective study

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dc.contributor.authorCheurfa, Nadir
dc.contributor.authorBrenner, Guilherme M.
dc.contributor.authorReis, André Fernandes [UNIFESP]
dc.contributor.authorDubois-Laforgue, Daniele
dc.contributor.authorRoussel, Ronan
dc.contributor.authorTichet, Jean
dc.contributor.authorLantieri, Olivier
dc.contributor.authorBalkau, Beverley
dc.contributor.authorFumeron, Frederic
dc.contributor.authorTimsit, José
dc.contributor.authorMarre, Michel
dc.contributor.authorVelho, Gilberto
dc.contributor.institutionUniv Paris 07
dc.contributor.institutionFed Univ Hlth Sci Porto Alegre
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionAssistance Publ Hop Paris Cochin Hosp
dc.contributor.institutionUniv Paris 05
dc.contributor.institutionAssistance Publ Hop Paris Bichat Hosp
dc.contributor.institutionInst Inter Reg Sante IRSA
dc.contributor.institutionINSERM
dc.contributor.institutionUniv Paris 11
dc.date.accessioned2016-01-24T14:06:15Z
dc.date.available2016-01-24T14:06:15Z
dc.date.issued2011-03-01
dc.description.abstractWe investigated associations of allelic variations in the WFS1 gene with insulin secretion and risk of type 2 diabetes in a general population prospective study.We studied 5,110 unrelated French men and women who participated in the prospective Data from Epidemiological Study on the Insulin Resistance Syndrome (DESIR) study. Additional cross-sectional analyses were performed on 4,472 French individuals with type 2 diabetes and 3,065 controls. Three single nucleotide polymorphisms (SNPs) were genotyped: rs10010131, rs1801213/rs7672995 and rs734312.We observed statistically significant associations between the major alleles of the three variants and prevalent type 2 diabetes in the DESIR cohort at baseline. Cox analyses showed an association between the G-allele of rs10010131 and incident type 2 diabetes (HR 1.34, 95% CI 1.08-1.70, p = 0.007). Similar results were observed for the G-allele of rs1801213 and the A-allele of rs734312. the GGA haplotype was associated with an increased risk of diabetes as compared with the ACG haplotype (HR 1.26, 95% CI 1.04-1.42, p = 0.02). We also observed statistically significant associations of the three SNPs with plasma glucose, HbA(1c) levels and insulin secretion at baseline and throughout the study in individuals with type 2 diabetes or at risk of developing diabetes. However, no association was observed in those who remained normoglycaemic at the end of the follow-up. Associations between the three variants and type 2 diabetes were replicated in cross-sectional studies of type 2 diabetic patients in comparison with a non-diabetic control group.The most frequent haplotype at the haplotype block containing the WFS1 gene modulated insulin secretion and was associated with an increased risk of type 2 diabetes.en
dc.description.affiliationUniv Paris 07, INSERM, Res Unit 695, F-75018 Paris, France
dc.description.affiliationFed Univ Hlth Sci Porto Alegre, Postgradut Program Hlth Sci, Porto Alegre, RS, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Mol Endocrinol Lab, São Paulo, Brazil
dc.description.affiliationAssistance Publ Hop Paris Cochin Hosp, Dept Immunol & Diabetol, Paris, France
dc.description.affiliationUniv Paris 05, UFR Med, Paris, France
dc.description.affiliationUniv Paris 07, UFR Med, Paris, France
dc.description.affiliationAssistance Publ Hop Paris Bichat Hosp, Dept Endocrinol Diabetol & Nutr, Paris, France
dc.description.affiliationInst Inter Reg Sante IRSA, La Riche, France
dc.description.affiliationINSERM, U1018, CESP, Ctr Res Epidemiol & Populat Hlth, Villejuif, France
dc.description.affiliationUniv Paris 11, UMRS 1018, Villejuif, France
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Mol Endocrinol Lab, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipSociete Francophone du Diabete (SFD - Alfediam)
dc.description.sponsorshipAssociation Diabete Risque Vasculaire (ADRV), France
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipINSERM
dc.description.sponsorshipCNAMTS
dc.description.sponsorshipLilly
dc.description.sponsorshipNovartis Pharma
dc.description.sponsorshipSanofi-Aventis
dc.description.sponsorshipINSERM (Reseaux en Sante Publique, Interactions entre les determinants de la sante)
dc.description.sponsorshipAssociation Diabete Risque Vasculaire
dc.description.sponsorshipFederation Francaise de Cardiologie
dc.description.sponsorshipLa Fondation de France
dc.description.sponsorshipALFEDIAM
dc.description.sponsorshipONIVINS
dc.description.sponsorshipArdix Medical
dc.description.sponsorshipBayer Diagnostics
dc.description.sponsorshipBecton Dickinson
dc.description.sponsorshipCardionics
dc.description.sponsorshipMerck Sante
dc.description.sponsorshipNovo Nordisk
dc.description.sponsorshipPierre Fabre
dc.description.sponsorshipRoche
dc.description.sponsorshipTopcon
dc.description.sponsorshipIDCAPES: 1798-09-0
dc.format.extent554-562
dc.identifierhttp://dx.doi.org/10.1007/s00125-010-1989-0
dc.identifier.citationDiabetologia. New York: Springer, v. 54, n. 3, p. 554-562, 2011.
dc.identifier.doi10.1007/s00125-010-1989-0
dc.identifier.issn0012-186X
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/33507
dc.identifier.wosWOS:000286987000013
dc.language.isoeng
dc.publisherSpringer
dc.relation.ispartofDiabetologia
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.rights.licensehttp://www.springer.com/open+access/authors+rights?SGWID=0-176704-12-683201-0
dc.subjectEndoplasmic reticulum stressen
dc.subjectGenetic epidemiologyen
dc.subjectPopulation studiesen
dc.subjectWolframinen
dc.titleDecreased insulin secretion and increased risk of type 2 diabetes associated with allelic variations of the WFS1 gene: the Data from Epidemiological Study on the Insulin Resistance Syndrome (DESIR) prospective studyen
dc.typeinfo:eu-repo/semantics/article
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