A polymorphism within the G6PC2 gene is associated with fasting plasma glucose levels by Bouatia-Naji Nabila, Rocheleau Ghislain, Van Lommel Leentje, Lemaire Katleen, Schuit Frans, Cavalcanti-Proença Christine, Marchand Marion, Hartikainen Anna-Liisa, Sovio Ulla, De Graeve Franck, Rung Johan, Vaxillaire Martine, Tichet Jean, Marre Michel, Balkau Beverley, Weill Jacques, Elliott Paul, Jarvelin Marjo-Riitta, Meyre David, Polychronakos Constantin, Dina Christian, Sladek Robert, Froguel Philippe in Science (New York, N.Y.) (2008). PubMed

Abstract

Several studies have shown that healthy individuals with fasting plasma glucose (FPG) levels at the high end of the normal range have an increased risk of mortality. To identify genetic determinants that contribute to interindividual variation in FPG, we tested 392,935 single-nucleotide polymorphisms (SNPs) in 654 normoglycemic participants for association with FPG, and we replicated the most strongly associated SNP (rs560887, P = 4 x 10(-7)) in 9353 participants. SNP rs560887 maps to intron 3 of the G6PC2 gene, which encodes glucose-6-phosphatase catalytic subunit-related protein (also known as IGRP), a protein selectively expressed in pancreatic islets. This SNP was associated with FPG (linear regression coefficient beta = -0.06 millimoles per liter per A allele, combined P = 4 x 10(-23)) and with pancreatic beta cell function (Homa-B model, combined P = 3 x 10(-13)) in three populations; however, it was not associated with type 2 diabetes risk. We speculate that G6PC2 regulates FPG by modulating the set point for glucose-stimulated insulin secretion in pancreatic beta cells.

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