Association of Pro12Ala PPAR-γ gene polymorphism with Graves' orbitopathy
Jacek Daroszewski1, Edyta Pawlak2, Marek Bolanowski1 & Irena Frydecka2,3
Introduction: Peroxisome proliferation-activated receptors-γ (PPAR-γ) have been shown to be involved in adipogenesis as well as in immunoregulation and inflammation control. Orbital fibroblast differentiation to adipocytes is a PPAR-γ dependent process essential for pathogenic tissue remodeling in Graves orbitopathy (GO).
Purpose: We studied the occurrence and possible associations of the Pro115Gln and Pro12Ala in the PPARγ2 gene with clinical manifestation of GO.
Material and methods: The Pro12Ala and Pro115Gln polymorphisms were examined using PCR-RFLP technique with restriction enzymes: HpaII and HincII, respectively, in 202 Graves disease patients. There were 168 patients with GO and 34 subjects without eye changes. Patients with GO were grouped according to the stage of the disease severity.
Results: We found that Ala allele and (Pro12Ala+Ala12Ala) genotype decreased the risk of OT by a factor of 3.33 and 3.45 (P=0.0002, 95% CI: 0.160.59 and P=0.001, 95% CI: 0.130.63, respectively). Moreover, the Ala12Ala genotype was not observed in the group of patients with GO. The patients heterozygous at this polymorphic site were significantly more frequent in a group of patients without GO as compared to GO group (38.2 vs 18.5%, P=0.01, 95% CI: 0.170.81). However, this polymorphism was not associated with a stage of GO.
The Pro115Gln mutation was not found in any of subjects examined.
Conclusions: We found that the Ala variant in Pro12Ala polymorphism is associated with decreased risk of GO and may be considered as a protective factor.