Interaction of DIO2 T92A and PPARγ2 P12A polymorphisms in the modulation of metabolic syndrome

被引：21

作者：

Fiorito, Mirella ^{[1
]}

Torrente, Isabella ^{[1
]}

De Cosmo, Salvatore ^{[2
]}

Guida, Valentina ^{[1
,3
]}

Colosimo, Alessia ^{[1
,5
]}

Prudente, Sabrina ^{[1
,2
]}

Flex, Elisabetta ^{[1
,3
]}

Menghini, Rossella ^{[6
]}

Miccoli, Roberto

Penno, Giuseppe

Pellegrini, Fabio

Tassi, Vittorio ^{[2
]}

Federici, Massimo ^{[6
]}

Trischitta, Vincenzo ^{[1
,2
,3
,4
]}

Dallapiccola, Bruno ^{[1
,3
]}

机构：

[1] CSS Mendel Inst, I-00198 Rome, Italy

[2] CSS Inst, Res Lab Diabetes & Endocrinol, San Giovanni Rotondo, Italy

[3] Sapienza Univ, Dept Expt Med & Pathol, Rome, Italy

[4] Sapienza Univ, Dept Clin Sci, Rome, Italy

[5] Univ Teramo, Dept Compared Biomed Sci, Teramo, Italy

[6] Univ Roma Tor Vergata, Dept Internal Med, Rome, Italy

来源：

OBESITY | 2007年 / 15卷 / 12期

关键词：

abdominal obesity; blood pressure; genetic susceptibility; insulin resistance; coronary artery disease;

D O I：

10.1038/oby.2007.343

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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) gamma 2 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 PPAR gamma 2 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 PPAR gamma 2 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.

引用

页码：2889 / 2895

页数：7