AHSG Tag Single Nucleotide Polymorphisms Associate With Type 2 Diabetes and Dyslipidemia

Studies of Metabolic Traits in 7,683 White Danish Subjects

  1. Gitte Andersen1,
  2. Kristoffer Sølvsten Burgdorf1,
  3. Thomas Sparsø1,
  4. Knut Borch-Johnsen123,
  5. Torben Jørgensen2,
  6. Torben Hansen1 and
  7. Oluf Pedersen13
  1. 1Steno Diabetes Center, Gentofte, Denmark
  2. 2Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark
  3. 3Faculty of Health Science, University of Aarhus, Aarhus, Denmark
  1. Corresponding author: Gitte Andersen, MSc, PhD, Steno Diabetes Center, Niels Steensens Vej 1, NLC2.12, DK-2820 Gentofte, Denmark. E-mail: gtta{at}steno.dk

Abstract

OBJECTIVE—The gene encoding the α2 Heremans-Schmid glycoprotein (AHSG) is a credible biological and positional candidate gene for type 2 diabetes and the metabolic syndrome, and previous attempts to relate AHSG variation with type 2 diabetes and obesity in Swedish and French Caucasians have been largely successful. We related seven frequent AHSG tag single nucleotide polymorphisms to a range of metabolic traits, including type 2 diabetes, obesity, and dyslipidemia.

RESEARCH DESIGN AND METHODS—The polymorphisms were genotyped in 7,683 white Danish subjects using Taqman allelic discrimination or chip-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, providing a statistical power of >99% to replicate previous findings. Data were analyzed in case-control and haplotype settings, and quantitative metabolic traits were examined for association. Moreover, epistatic effects between AHSG variants and insulin receptor substrate-1 (IRS1) and β-2-adrenergic receptor polymorphisms were investigated.

RESULTS—The −469T>G (rs2077119) and IVS6+98C>T (rs2518136) polymorphisms were associated with type 2 diabetes (P = 0.007 and P = 0.006, respectively, or Pcorr = 0.04 and Pcorr = 0.03, respectively, following correction for multiple hypothesis testing), and in a combined analysis of the present and a previous study −469T>G remained significant (odds ratio 0.90 [95% CI 0.84–0.97]; P = 0.007). Furthermore, two AHSG haplotypes were associated with dyslipidemia (P = 0.003 and Pcorr = 0.009). Thr248Met (rs4917) tended to associate with lower fasting and post–oral glucose tolerance test serum insulin release (P = 0.02, Pcorr = 0.1 for fasting and P = 0.04, Pcorr = 0.2 for area under the insulin curve) and improved insulin sensitivity estimated by the homeostasis model assessment of insulin resistance (9.0 vs. 8.6 mmol · l−1 · pmol−1 · l−1; P = 0.01, Pcorr = 0.06). Indications of epistatic effects of AHSG variants with the IRS1 Gly971Arg polymorphism were observed for fasting serum triglyceride concentrations.

CONCLUSIONS—Based on present and previous findings, common variation in AHSG may contribute to the interindividual variation in metabolic traits.

Footnotes

  • Published ahead of print at http://diabetes.diabetesjournals.org on 3 March 2008. DOI: 10.2337/db07-0558.

    Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/db07-0558.

    G.A. holds stock in Novo Nordisk.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted February 7, 2008.
    • Received April 25, 2007.
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  1. Diabetes vol. 57 no. 5 1427-1432
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