Metabolism - Clinical and Experimental
Volume 60, Issue 5 , Pages 655-663, May 2011

The APOE −219G/T and +113G/C polymorphisms affect insulin resistance among Turks

  • Evrim Komurcu-Bayrak

      Affiliations

    • Department of Genetics, Institute for Experimental Medicine, Istanbul University, 34080, Istanbul, Turkey
    • Corresponding Author InformationCorresponding author.
    • ,
  • Altan Onat

      Affiliations

    • Department of Cardiology, Cerrahpasa Medical Faculty, Istanbul University, 34099, Istanbul, Turkey
    • ,
  • Berna Yuzbasiogullari

      Affiliations

    • Department of Genetics, Institute for Experimental Medicine, Istanbul University, 34080, Istanbul, Turkey
    • Department of Clinical Chemistry, Tampere University Hospital and University of Tampere, Medical School, 33521, Tampere, Finland
    • ,
  • Nina Mononen

      Affiliations

    • Department of Clinical Chemistry, Tampere University Hospital and University of Tampere, Medical School, 33521, Tampere, Finland
    • ,
  • Reijo Laaksonen

      Affiliations

    • Department of Clinical Chemistry, Tampere University Hospital and University of Tampere, Medical School, 33521, Tampere, Finland
    • ,
  • Mika Kähönen

      Affiliations

    • Department of Clinical Physiology, Tampere University Hospital and University of Tampere, Medical School, 33521, Tampere, Finland
    • ,
  • Gulay Hergenc

      Affiliations

    • Department of Biology, Yildiz Technical University, 34349, Istanbul, Turkey
    • ,
  • Terho Lehtimäki

      Affiliations

    • Department of Clinical Chemistry, Tampere University Hospital and University of Tampere, Medical School, 33521, Tampere, Finland
    • ,
  • Nihan Erginel-Unaltuna

      Affiliations

    • Department of Genetics, Institute for Experimental Medicine, Istanbul University, 34080, Istanbul, Turkey

Received 26 March 2010; accepted 22 June 2010. published online 19 August 2010.

Abstract 

The −219G/T (rs405509) and +113G/C (rs440446) polymorphisms within the regulatory region of the apolipoprotein E (APOE) gene have been related to the transcriptional activity of the gene. We examined the effect of the stated polymorphisms and their construct haplotypes with the APOE ɛ2/ɛ3/ɛ4 polymorphism on lipid levels and insulin resistance in the Turkish Adult Risk Factor Study. Randomly selected 1774 adults (mean age, 55.0 ± 11.7 years; 51.2% women) participating in the population-based Turkish Adult Risk Factor Study were cross-sectionally analyzed for the −219G/T, +113G/C, and ɛ2/ɛ3/ɛ4 polymorphisms as well as their haplotypes. Insulin resistance was defined as the 70th percentile in the sample (>2.51) of the homeostatic model assessment (HOMA). The frequencies of the −219T and +113C alleles were 0.477 and 0.423, respectively; and those of haplotype 1 (GGɛ3) and haplotype 2 (TCɛ3) were 44.1% and 41.9%, respectively. The −219G/T and +113G/C genotypes (both P < .04) and diplotypes of haplotype 2 (TCɛ3) (P < .014) were inversely related to serum fasting insulin and the HOMA index, even after controlling for 8 relevant covariates, but not to serum lipids. Within the APOE3 group, haplotype 2 (TC−/TC+) heterozygotes had an odds ratio of 0.66 (95% confidence interval, 0.42-0.99) for HOMA of insulin resistance after adjusting for 8 covariates. APOE promoter polymorphisms and their diplotypes are independently related with serum fasting insulin levels and HOMA index among Turks.

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 Study subjects were unrelated and gave written consent to participate in the study after being informed of its nature. The study protocol was approved by the Ethics Committee of the Istanbul Medical Faculty, Istanbul University.

 EKB wrote the manuscript, carried out the experimental work, and performed the statistical analyses; AO initiated the study and participated in its design as well as the coordination and collection of clinical data, in addition to editing the manuscript; BY and NM assisted in planning the study and participated in the experimental work; RL and MK assisted in planning the study and drafting the manuscript; GH carried out the biochemical experimental work and edited the manuscript; TL and NEU were responsible for the molecular genetic studies and participated in planning the study and drafting the manuscript.

PII: S0026-0495(10)00203-9

doi:10.1016/j.metabol.2010.06.016

Metabolism - Clinical and Experimental
Volume 60, Issue 5 , Pages 655-663, May 2011

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