A polymorphism within the G6PC2 gene is associated with fasting plasma glucose levels.
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.
Bouatia-Naji
Nabila
N
CNRS UMR 8090 Institute of Biology, Pasteur Institute of Lille and Lille 2 Droit et Santé University, 59019 Lille, France.
Rocheleau
Ghislain
G
Van Lommel
Leentje
L
Lemaire
Katleen
K
Schuit
Frans
F
Cavalcanti-Proença
Christine
C
Marchand
Marion
M
Hartikainen
Anna-Liisa
AL
Sovio
Ulla
U
De Graeve
Franck
F
Rung
Johan
J
Vaxillaire
Martine
M
Tichet
Jean
J
Marre
Michel
M
Balkau
Beverley
B
Weill
Jacques
J
Elliott
Paul
P
Jarvelin
Marjo-Riitta
MR
Meyre
David
D
Polychronakos
Constantin
C
Dina
Christian
C
Sladek
Robert
R
Froguel
Philippe
P
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
D001786:Blood Glucose; D007328:Insulin; D005952:Glucose-6-Phosphatase; C492194:G6PC2 protein, human