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?
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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? / Poulsen, Pernille; Andersen, Gitte; Fenger, Mogens; Hansen, Torben; Echwald, Søren Morgenthaler; Vølund, Aage; Beck-Nielsen, Henning; Pedersen, Oluf; Vaag, Allan.
In: Diabetes, Vol. 52, No. 1, 2003, p. 194-8.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Impact of two common polymorphisms in the PPARgamma gene on glucose tolerance and plasma insulin profiles in monozygotic and dizygotic twins
T2 - thrifty genotype, thrifty phenotype, or both?
AU - Poulsen, Pernille
AU - Andersen, Gitte
AU - Fenger, Mogens
AU - Hansen, Torben
AU - Echwald, Søren Morgenthaler
AU - Vølund, Aage
AU - Beck-Nielsen, Henning
AU - Pedersen, Oluf
AU - Vaag, Allan
PY - 2003
Y1 - 2003
N2 - 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.
AB - 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.
KW - Aged
KW - Alleles
KW - Gene Frequency
KW - Genetic Variation
KW - Genotype
KW - Glucose
KW - Glucose Intolerance
KW - Humans
KW - Insulin
KW - Phenotype
KW - Polymorphism, Genetic
KW - Receptors, Cytoplasmic and Nuclear
KW - Transcription Factors
KW - Twins, Dizygotic
KW - Twins, Monozygotic
M3 - Journal article
C2 - 12502512
VL - 52
SP - 194
EP - 198
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 1
ER -
ID: 38457785