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
CNRS UMR 8090 Institute of Biology, Pasteur Institute of Lille and Lille 2 Droit et Santé University, 59019 Lille, France.
Science. 2008 May 23;320(5879):1085-8. doi: 10.1126/science.1156849. Epub 2008 May 1.
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.
多项研究表明，空腹血糖（FPG）水平处于正常范围上限的健康个体死亡风险增加。为了确定导致FPG个体间差异的遗传决定因素，我们在654名血糖正常的参与者中检测了392,935个单核苷酸多态性（SNP）与FPG的关联性，并在9353名参与者中重复验证了关联性最强的SNP（rs560887，P = 4×10⁻⁷）。SNP rs560887定位于G6PC2基因的内含子3，该基因编码葡萄糖-6-磷酸酶催化亚基相关蛋白（也称为IGRP），一种在胰岛中选择性表达的蛋白质。在三个人群中，该SNP与FPG相关（线性回归系数β = -0.06毫摩尔/升/每个A等位基因，合并P = 4×10⁻²³），并与胰腺β细胞功能相关（Homa-B模型，合并P = 3×10⁻¹³）；然而，它与2型糖尿病风险无关。我们推测，G6PC2通过调节胰腺β细胞中葡萄糖刺激的胰岛素分泌的设定点来调节FPG。
