Impact of two common polymorphisms in the PPARgamma gene on glucose tolerance and plasma insulin profiles in monozygotic and dizygotic twins: thrifty genotype, thrifty phenotype, or both?

Pernille Poulsen, Gitte Andersen, Mogens Fenger, Torben Hansen, Søren M Echwald, Aage Vølund, Henning Beck-Nielsen, Oluf Pedersen, Allan Vaag

    Publikation: Bidrag til tidsskriftArtikelForskningpeer review

    Abstrakt

    The Pro12Ala polymorphism in the PPARgamma2 gene has been associated with reduced risk of type 2 diabetes and insulin resistance. Recently, an association between dizygotic twinning and PPARgamma gene polymorphisms has been proposed. We investigated the phenotypic appearance of the two polymorphisms (Pro12Ala and exon 6 C-->T) in PPARgamma among elderly twins (207 monozygotic [MZ] and 342 dizygotic [DZ]) and evaluated whether they could explain previously reported differences in plasma glucose and insulin profiles among MZ and DZ twins. We demonstrated a significant impact of the Pro12Ala polymorphism on glucose tolerance, diabetic status, homeostasis model assessment for insulin resistance, and plasma insulin profiles in twins. No impact of the silent exon 6 polymorphism on glucose homeostasis or plasma insulin profiles was found. Independent of the polymorphisms, we observed a significant impact of zygosity status per se on the plasma insulin profile after oral glucose ingestion, with the MZ twins being more hyperinsulinemic, indicating insulin resistance, than the DZ twins. Nonsignificantly higher glucose concentrations were observed among MZ compared with DZ twins. We demonstrated an association between the Ala allele and reduced risk of diabetes and insulin resistance in twins. However, the differences in metabolic profiles among MZ and DZ twins were not explained by differences in frequencies of the genetic variants and may be due to intrauterine environmental factors operating in twins independent of genotype. Accordingly, our study simultaneously supports a role for both the intrauterine environment (thrifty phenotype) and for genetics (thrifty genotype) in the etiology of insulin resistance and perhaps glucose intolerance in twins.

    OriginalsprogEngelsk
    Sider (fra-til)194-198
    Antal sider5
    TidsskriftDiabetes
    Vol/bind52
    Udgave nummer1
    DOI
    StatusUdgivet - jan. 2003

    Fingeraftryk Udforsk hvilke forskningsemner 'Impact of two common polymorphisms in the PPARgamma gene on glucose tolerance and plasma insulin profiles in monozygotic and dizygotic twins: thrifty genotype, thrifty phenotype, or both?' indeholder.

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