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Elsevier, Year Book of Endocrinology, (2012), p. 13

DOI: 10.1016/j.yend.2012.03.063

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Genome-Wide Association Identifies Nine Common Variants Associated With Fasting Proinsulin Levels and Provides New Insights Into the Pathophysiology of Type 2 Diabetes

Journal article published in 2011 by J.-A. (John-Anker) Zwart, J. B. van Meurs, F. van't Hooft, W. (Weihua) Zhang, S. (Sophie) van Wingerden, J. (Joanna) Yang, T.-P. (Tsun-Po) Yang, T.-P. Yang, Me E. Travers, C. J. Wille, Rona J. (Rona) Strawbridge, T. W. Winkle, A. R. Woo, E. (Eleftheria) Zeggini, Bj Zethelius and other authors.
This paper is available in a repository.
This paper is available in a repository.

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Data provided by SHERPA/RoMEO

Abstract

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired beta-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 approximately 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