A polymorphism within the G6PC2 gene is associated with fasting plasma glucose levels

Nabila Bouatia-Naji; Ghislain Rocheleau; Leentje Van Lommel; Katleen Lemaire; Frans Schuit; Christine Cavalcanti-Proença; Marion Marchand; Anna Liisa Hartikainen; Ulla Sovio; Franck De Graeve; Johan Rung; Martine Vaxillaire; Jean Tichet; Michel Marre; Beverley Balkau; Jacques Weill; Paul Elliott; Marjo Riitta Jarvelin; David Meyre; Constantin Polychronakos; Christian Dina; Robert Sladek; Philippe Froguel

doi:10.1126/science.1156849

A polymorphism within the G6PC2 gene is associated with fasting plasma glucose levels

Nabila Bouatia-Naji, Ghislain Rocheleau, Leentje Van Lommel, Katleen Lemaire, Frans Schuit, Christine Cavalcanti-Proença, Marion Marchand, Anna Liisa Hartikainen, Ulla Sovio, Franck De Graeve, Johan Rung, Martine Vaxillaire, Jean Tichet, Michel Marre, Beverley Balkau, Jacques Weill, Paul Elliott, Marjo Riitta Jarvelin, David Meyre, Constantin PolychronakosChristian Dina, Robert Sladek, Philippe Froguel

Research output: Contribution to journal › Article › peer-review

201 Scopus citations

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 × 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 β = -0.06 millimoles per liter per A allele, combined P = 4 × 10 ^-23) and with pancreatic β cell function (Homa-B model, combined P = 3 × 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 β cells.

Original language	English
Pages (from-to)	1085-1088
Number of pages	4
Journal	Science
Volume	320
Issue number	5879
DOIs	https://doi.org/10.1126/science.1156849
State	Published - 23 May 2008
Externally published	Yes

Access to Document

10.1126/science.1156849

Cite this

Bouatia-Naji, N., Rocheleau, G., Van Lommel, L., Lemaire, K., Schuit, F., Cavalcanti-Proença, C., Marchand, M., Hartikainen, A. L., Sovio, U., De Graeve, F., Rung, J., Vaxillaire, M., Tichet, J., Marre, M., Balkau, B., Weill, J., Elliott, P., Jarvelin, M. R., Meyre, D., ... Froguel, P. (2008). A polymorphism within the G6PC2 gene is associated with fasting plasma glucose levels. Science, 320(5879), 1085-1088. https://doi.org/10.1126/science.1156849

@article{5ccaa9ade2b841b1915c1892b2f89268,

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 × 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 β = -0.06 millimoles per liter per A allele, combined P = 4 × 10 -23) and with pancreatic β cell function (Homa-B model, combined P = 3 × 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 β cells.",

author = "Nabila Bouatia-Naji and Ghislain Rocheleau and {Van Lommel}, Leentje and Katleen Lemaire and Frans Schuit and Christine Cavalcanti-Proen{\c c}a and Marion Marchand and Hartikainen, {Anna Liisa} and Ulla Sovio and {De Graeve}, Franck and Johan Rung and Martine Vaxillaire and Jean Tichet and Michel Marre and Beverley Balkau and Jacques Weill and Paul Elliott and Jarvelin, {Marjo Riitta} and David Meyre and Constantin Polychronakos and Christian Dina and Robert Sladek and Philippe Froguel",

year = "2008",

month = may,

day = "23",

doi = "10.1126/science.1156849",

language = "English",

volume = "320",

pages = "1085--1088",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "5879",

}

Bouatia-Naji, N, Rocheleau, G, Van Lommel, L, Lemaire, K, Schuit, F, Cavalcanti-Proença, C, Marchand, M, Hartikainen, AL, Sovio, U, De Graeve, F, Rung, J, Vaxillaire, M, Tichet, J, Marre, M, Balkau, B, Weill, J, Elliott, P, Jarvelin, MR, Meyre, D, Polychronakos, C, Dina, C, Sladek, R & Froguel, P 2008, 'A polymorphism within the G6PC2 gene is associated with fasting plasma glucose levels', Science, vol. 320, no. 5879, pp. 1085-1088. https://doi.org/10.1126/science.1156849

TY - JOUR

T1 - A polymorphism within the G6PC2 gene is associated with fasting plasma glucose levels

AU - Bouatia-Naji, Nabila

AU - Rocheleau, Ghislain

AU - Van Lommel, Leentje

AU - Lemaire, Katleen

AU - Schuit, Frans

AU - Cavalcanti-Proença, Christine

AU - Marchand, Marion

AU - Hartikainen, Anna Liisa

AU - Sovio, Ulla

AU - De Graeve, Franck

AU - Rung, Johan

AU - Vaxillaire, Martine

AU - Tichet, Jean

AU - Marre, Michel

AU - Balkau, Beverley

AU - Weill, Jacques

AU - Elliott, Paul

AU - Jarvelin, Marjo Riitta

AU - Meyre, David

AU - Polychronakos, Constantin

AU - Dina, Christian

AU - Sladek, Robert

AU - Froguel, Philippe

PY - 2008/5/23

Y1 - 2008/5/23

N2 - 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 × 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 β = -0.06 millimoles per liter per A allele, combined P = 4 × 10 -23) and with pancreatic β cell function (Homa-B model, combined P = 3 × 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 β cells.

AB - 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 × 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 β = -0.06 millimoles per liter per A allele, combined P = 4 × 10 -23) and with pancreatic β cell function (Homa-B model, combined P = 3 × 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 β cells.

UR - http://www.scopus.com/inward/record.url?scp=44449091627&partnerID=8YFLogxK

U2 - 10.1126/science.1156849

DO - 10.1126/science.1156849

M3 - Article

C2 - 18451265

AN - SCOPUS:44449091627

SN - 0036-8075

VL - 320

SP - 1085

EP - 1088

JO - Science

JF - Science

IS - 5879

ER -

A polymorphism within the G6PC2 gene is associated with fasting plasma glucose levels

Abstract

Access to Document

Fingerprint

Cite this