title: Interaction of DIO2 T92A and PPARgamma2 P12A polymorphisms in the modulation of metabolic syndrome.
abstract: Type 2 iodothyronine deiodinase (DIO2) converts thyroid prohormone tetraiodothyronine into the biologically active triiodothyronine hormone, which increases insulin sensitivity at the skeletal muscle level. The DIO2 T92A polymorphism modulates deiodinase activity and has been inconsistently associated with insulin resistance. Also, the P121A polymorphism of the peroxisome proliferator-activated receptor (PPAR) gamma2 gene, which encodes a transcription factor involved in insulin signaling, has been inconsistently associated with insulin resistance. This study was aimed at evaluating the combined effect of DIO2 T92A and PPARgamma2 P12A polymorphisms on insulin resistance-related features in 590 non-diabetic whites. A significant gene-gene interaction was observed in the modulation of systolic (p = 0.01) and diastolic (p = 0.02) blood pressure and metabolic syndrome (p = 0.02), with carriers of both DIO2 A92 and PPARgamma2 A12 variants showing the worst phenotype. This latter interaction was also shown by multifactor dimensionality reduction analysis (p = 0.0045). A peroxisome proliferator response element in the DIO2 promoter was identified by in silico analysis and confirmed by in vitro gel shift mobility assay, thus providing a biological plausibility for the observed gene-gene interaction. If confirmed in other populations, comprising several thousand individuals, these data may help identify individuals at risk for insulin resistance-related abnormalities.
authors.affiliation: CSS-Mendel Institute, viale Regina Margherita, 261, 00198 Roma, Italy.
authors.forename: Mirella
authors.initials: M
authors.lastname: Fiorito
authors.forename: Isabella
authors.initials: I
authors.lastname: Torrente
authors.forename: Salvatore
authors.initials: S
authors.lastname: De Cosmo
authors.forename: Valentina
authors.initials: V
authors.lastname: Guida
authors.forename: Alessia
authors.initials: A
authors.lastname: Colosimo
authors.forename: Sabrina
authors.initials: S
authors.lastname: Prudente
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Flex
authors.forename: Rossella
authors.initials: R
authors.lastname: Menghini
authors.forename: Roberto
authors.initials: R
authors.lastname: Miccoli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Penno
authors.forename: Fabio
authors.initials: F
authors.lastname: Pellegrini
authors.forename: Vittorio
authors.initials: V
authors.lastname: Tassi
authors.forename: Massimo
authors.initials: M
authors.lastname: Federici
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Trischitta
authors.forename: Bruno
authors.initials: B
authors.lastname: Dallapiccola
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D006973:Hypertension / Q000235:genetics; D007333:Insulin Resistance / Q000235:genetics; D007453:Iodide Peroxidase / Q000235:genetics*; D007558:Italy; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics*; D008875:Middle Aged; D009765:Obesity / Q000235:genetics; D047495:PPAR gamma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D007453:Iodide Peroxidase; D047495:PPAR gamma; D000097564:Iodothyronine Deiodinase Type II