RGD Reference Report - Interaction of DIO2 T92A and PPARgamma2 P12A polymorphisms in the modulation of metabolic syndrome. - Rat Genome Database

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Interaction of DIO2 T92A and PPARgamma2 P12A polymorphisms in the modulation of metabolic syndrome.

Authors: Fiorito, M  Torrente, I  De Cosmo, S  Guida, V  Colosimo, A  Prudente, S  Flex, E  Menghini, R  Miccoli, R  Penno, G  Pellegrini, F  Tassi, V  Federici, M  Trischitta, V  Dallapiccola, B 
Citation: Fiorito M, etal., Obesity (Silver Spring). 2007 Dec;15(12):2889-95.
RGD ID: 2313696
Pubmed: PMID:18198294   (View Abstract at PubMed)
DOI: DOI:10.1038/oby.2007.343   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
DIO2HumanMetabolic Syndrome  IAGP DNA:polymorphism: :p.T92A (human)RGD 
Dio2RatMetabolic Syndrome  ISODIO2 (Homo sapiens)DNA:polymorphism: :p.T92A (human)RGD 
Dio2MouseMetabolic Syndrome  ISODIO2 (Homo sapiens)DNA:polymorphism: :p.T92A (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Dio2  (iodothyronine deiodinase 2)

Genes (Mus musculus)
Dio2  (deiodinase, iodothyronine, type II)

Genes (Homo sapiens)
DIO2  (iodothyronine deiodinase 2)


Additional Information