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A −30G>A Polymorphism of the β-Cell–Specific Glucokinase Promoter Associates With Hyperglycemia in the General Population of Whites

  1. Christian S. Rose1,
  2. Jakob Ek1,
  3. Søren A. Urhammer1,
  4. Charlotte Glümer12,
  5. Knut Borch-Johnsen13,
  6. Torben Jørgensen2,
  7. Oluf Pedersen13 and
  8. Torben Hansen1
  1. 1Steno Diabetes Center and Hagedorn Research Institute, Copenhagen, Denmark
  2. 2Centre of Preventive Medicine, Glostrup University Hospital, Glostrup, Denmark
  3. 3Faculty of Health Science, University of Aarhus, Aarhus, Denmark
  1. Address correspondence and reprint requests to Christian Schack Rose, MSc, Steno Diabetes Center, Niels Steensens Vej 8, NSP1.10, DK-2820 Gentofte, Denmark. E-mail: csro{at}steno.dk

Abstract

A graded relationship has been reported between fasting and postprandial plasma glucose levels and the subsequent risk of cardiovascular morbidity and mortality. We hypothesized that the GCK −30G>A promoter polymorphism is associated with elevated glycemia in the middle-aged general population of whites, as well as with features of the World Health Organization (WHO)-defined metabolic syndrome. The GCK −30G>A polymorphism was genotyped in the population-based Inter99 study cohort (5,965 subjects) and in 332 nondiabetic subjects and 1,063 patients with type 2 diabetes. In the Inter99 cohort, the GCK −30A allele was associated with increased fasting (P < 0.001) and post–oral glucose tolerance test (OGTT) plasma glucose levels (P < 0.001), and in the same cohort, the GCK −30A allele was more frequent among 1,325 subjects with the metabolic syndrome than among 1,679 subjects without any components of the metabolic syndrome (P = 0.002). Moreover, the GCK −30A allele frequency was higher among 2,587 subjects with impaired glucose regulation (IGR) than among 4,773 glucose-tolerant subjects (17.3% [95% CI 16.2–18.3] vs. 15.0% [14.3–15.7], P < 0.001, odds ratio GG vs. GA 1.21 [1.08–1.36], GG vs. AA 1.62 [1.17–2.24]). In conclusion, the GCK −30G>A polymorphism associates with elevated fasting and post-OGTT glycemia in the middle-aged general population of whites, as well as with IGR and other features of the WHO-defined metabolic syndrome.

Footnotes

    • Accepted June 27, 2005.
    • Received April 5, 2005.
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