title: A polymorphism within the G6PC2 gene is associated with fasting plasma glucose levels.
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.
authors.affiliation: CNRS UMR 8090 Institute of Biology, Pasteur Institute of Lille and Lille 2 Droit et Santé University, 59019 Lille, France.
authors.forename: Nabila
authors.initials: N
authors.lastname: Bouatia-Naji
authors.forename: Ghislain
authors.initials: G
authors.lastname: Rocheleau
authors.forename: Leentje
authors.initials: L
authors.lastname: Van Lommel
authors.forename: Katleen
authors.initials: K
authors.lastname: Lemaire
authors.forename: Frans
authors.initials: F
authors.lastname: Schuit
authors.forename: Christine
authors.initials: C
authors.lastname: Cavalcanti-Proença
authors.forename: Marion
authors.initials: M
authors.lastname: Marchand
authors.forename: Anna-Liisa
authors.initials: AL
authors.lastname: Hartikainen
authors.forename: Ulla
authors.initials: U
authors.lastname: Sovio
authors.forename: Franck
authors.initials: F
authors.lastname: De Graeve
authors.forename: Johan
authors.initials: J
authors.lastname: Rung
authors.forename: Martine
authors.initials: M
authors.lastname: Vaxillaire
authors.forename: Jean
authors.initials: J
authors.lastname: Tichet
authors.forename: Michel
authors.initials: M
authors.lastname: Marre
authors.forename: Beverley
authors.initials: B
authors.lastname: Balkau
authors.forename: Jacques
authors.initials: J
authors.lastname: Weill
authors.forename: Paul
authors.initials: P
authors.lastname: Elliott
authors.forename: Marjo-Riitta
authors.initials: MR
authors.lastname: Jarvelin
authors.forename: David
authors.initials: D
authors.lastname: Meyre
authors.forename: Constantin
authors.initials: C
authors.lastname: Polychronakos
authors.forename: Christian
authors.initials: C
authors.lastname: Dina
authors.forename: Robert
authors.initials: R
authors.lastname: Sladek
authors.forename: Philippe
authors.initials: P
authors.lastname: Froguel
mesh_terms: D000483:Alleles; D001786:Blood Glucose / Q000378:metabolism*; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005215:Fasting; D005260:Female; D020022:Genetic Predisposition to Disease; D005952:Glucose-6-Phosphatase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000502:physiology; D007438:Introns; D016014:Linear Models; D008297:Male; D015201:Meta-Analysis as Topic; D020641:Polymorphism, Single Nucleotide
chemical_list: D001786:Blood Glucose; D007328:Insulin; D005952:Glucose-6-Phosphatase; C492194:G6PC2 protein, human