Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes

OBJECTIVE - Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired b-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS - We have conducted a meta-analysis of genome-wide association tests of ;2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci... Mehr ...

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Verfasser: Strawbridge, R.J.
Dupuis, J.
Prokopenko, I.
Barker, A.
Ahlqvist, E.
Rybin, D.
Petrie, J.R.
Bouatia-Naji, N.
Dimas, A.S.
Nica, A.
Wheeler, E.
Chen, H.
Voight, B.F.
Taneera, J.
Kanoni, S.
Hottenga, J.J.
de Geus, E.J.C.
Willemsen, G.
Boomsma, D.I.
Forsen, T.J.
Clarke, R.
Franzosi, M.G.
Seedorf, U.
Watkins, H.
Froguel, P.
Johnson, P.
Deloukas, P.
Collins, F.S.
Laakso, M.
Dermitzakis, E.T.
Boehnke, M.
McCarthy, M.I.
Wareham, N.J.
Groop, L.
Pattou, F.
Gloyn, A.L.
Dedoussis, G.V.
Lyssenko, V.
Meigs, J.B.
Barroso, I.
Watanabe, R.M.
Ingelsson, E.
Langenberg, C.
Hamsten, A.
Florez, J.C.
Dokumenttyp: Artikel
Erscheinungsdatum: 2011
Reihe/Periodikum: Strawbridge , R J , Dupuis , J , Prokopenko , I , Barker , A , Ahlqvist , E , Rybin , D , Petrie , J R , Bouatia-Naji , N , Dimas , A S , Nica , A , Wheeler , E , Chen , H , Voight , B F , Taneera , J , Kanoni , S , Hottenga , J J , de Geus , E J C , Willemsen , G , Boomsma , D I , Forsen , T J , Clarke , R , Franzosi , M G , Seedorf , U , Watkins , H , Froguel , P , Johnson , P , Deloukas , P , Collins , F S , Laakso , M , Dermitzakis , E T , Boehnke , M , McCarthy , M I , Wareham , N J , Groop , L , Pattou , F , Gloyn , A L , Dedoussis , G V , Lyssenko , V , Meigs , J B , Barroso , I , Watanabe , R M , Ingelsson , E , Langenberg , C , Hamsten , A & Florez , J C 2011 , ' Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes ' , Diabetes , vol. 60 , no. 10 , pp. 2624-2634 . https://doi.org/10.2337/db11-0415
Schlagwörter: /dk/atira/pure/keywords/cohort_studies/netherlands_twin_register_ntr_ / name=Netherlands Twin Register (NTR) / /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being / name=SDG 3 - Good Health and Well-being
Sprache: Englisch
Permalink: https://search.fid-benelux.de/Record/base-27622748
Datenquelle: BASE; Originalkatalog
Powered By: BASE
Link(s) : https://research.vu.nl/en/publications/bc8ec347-6e39-43f8-ace2-13c038905116

OBJECTIVE - Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired b-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS - We have conducted a meta-analysis of genome-wide association tests of ;2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS - Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10