Variations in the G6PC2/ABCB11 genomic region are associated with fasting glucose levels

Wei Min Chen, Michael R. Erdos, Anne U. Jackson, Richa Saxena, Serena Sanna, Kristi D. Silver, Nicholas J. Timpson, Torben Hansen, Marco Orrù, Maria Grazia Piras, Lori L. Bonnycastle, Cristen J. Wilier, Valeriya Lyssenko, Haiqing Shen, Johanna Kuusisto, Shah Ebrahim, Natascia Sestu, William L. Duren, Maria Cristina Spada, Heather M. StringhamLaura J. Scott, Nazario Olla, Amy J. Swift, Samer Najjar, Braxton D. Mitchell, Debbie A. Lawlor, George Davey Smith, Yoav Ben-Shlomo, Gitte Andersen, Knut Borch-Johnsen, Torben Jørgensen, Jouko Saramies, Timo T. Valle, Thomas A. Buchanan, Alan R. Shuldiner, Edward Lakatta, Richard N. Bergman, Manuela Uda, Jaakko Tuomilehto, Oluf Pedersen, Antonio Cao, Leif Groop, Karen L. Mohlke, Markku Laakso, David Schlessinger, Francis S. Collins, David Altshuler, Gonçalo R. Abecasis, Michael Boehnke, Angelo Scuteri*, Richard M. Watanabe

*Corresponding author af dette arbejde

    Publikation: Bidrag til tidsskriftArtikelForskningpeer review


    Identifying the genetic variants that regulate fasting glucose concentrations may further our understanding of the pathogenesis of diabetes. We therefore investigated the association of fasting glucose levels with SNPs in 2 genomewide scans including a total of 5,088 nondiabetic individuals from Finland and Sardinia. We found a significant association between the SNP rs563694 and fasting glucose concentrations (P = 3.5 × 10 -7). This association was further investigated in an additional 18,436 nondiabetic individuals of mixed European descent from 7 different studies. The combined P value for association in these follow-up samples was 6.9 × 10 26, and combining results from all studies resulted in an overall P value for association of 6.4 × 10 -33. Across these studies, fasting glucose concentrations increased 0.01-0.16 mM with each copy of the major allele, accounting for approximately 1% of the total variation in fasting glucose. The rs563694 SNP is located between the genes glucose-6-phosphatase catalytic subunit 2 (G6PC2) and ATP-binding cassette, subfamily B (MDR/TAP), member 11 (ABCB11). Our results in combination with data reported in the literature suggest that G6PC2, a glucose-6-phosphatase almost exclusively expressed in pancreatic islet cells, may underlie variation in fasting glucose, though it is possible that ABCB11, which is expressed primarily in liver, may also contribute to such variation.

    Sider (fra-til)2620-2628
    Antal sider9
    TidsskriftJournal of Clinical Investigation
    Udgave nummer7
    StatusUdgivet - 1 jul. 2008


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