학술논문
A polymorphism within the G6PC2 gene is associated with fasting plasma glucose levels
REPORTS
REPORTS
Document Type
Author abstract
Report
Report
Author
Bouatia-Naji, Nabila; Rocheleau, Ghislain; Van Lommel, Leentje; Lemaire, Katleen; Schuit, Frans; Cavalcanti-Proenca, 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
Source
Science. May 23, 2008, Vol. 320 Issue 5879, p1085, 4 p.
Subject
Language
English
ISSN
0036-8075
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.sup.-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.sup.-23]) and with pancreatic [beta] cell function (Homa-B model, combined P = 3 x [10.sup.-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.