Association between polymorphic markers in candidate genes and the risk of manifestationof endocrine ophthalmopathy in patients with Graves’ disease

Abstract

Aim. To analyze the association between the polymorphic markers in CTLA4, TNF, IL10 and IL16 genes and the risk of manifestation of endocrine ophthalmopathy (EO) in patients with Graves’ disease (GD). Materials and methods. Case-control study included 248 patients with GD. Using polymerase chain reaction we studied the distribution of alleles and genotypes of polymorphic markers such as A60G (rs3087243) in CTLA4 gene, G(-308)A (rs1800629) in TNF gene, G(-1082)A (rs1800896) in IL10 gene, T3249C (rs4778641) in IL16 gene among 141 patients with Graves’ disease and EO and 107 patients with GD without EO. Results and discussion. The frequencies of A alleles and the AA genotypes were significantly increased and the frequencies of G alleles and the GG genotype polymorphic markers rs3087243 of CTLA4 gene and rs1800896 of IL10 gene, as well as the GG genotype polymorphic marker rs1800629 of TNF gene were reduced in patients with GD and EO. The polymorphism in CTLA4 gene was also associated with the activity and the severity of EO. The comparative analysis of the allele and genotype frequency distribution of polymorphic markers of IL16 gene did not show the significant difference. Conclusion. The risk of manifestation and the development of EO in patients with Graves’ disease can be caused by not only environmental, but also genetic risk factors.

The 4G/5G Polymorphism of Plasminogen Activator Inhibitor Type 1 is a Predictor of Moderate-to-Severe Thyroid Eye Disease

“…Data on PAI-1 polymorphisms in TED, up till now, have not been published, and only few candidate other genes have been studied in this respect. CTLA-4, 27 vitamin D receptor, 28 TNF, IL-10 29 and deiodinase-2 polymorphisms 30 were recently described in patient cohorts of comparable size. However, unlike these genes which are immune response related, PAI-1 acts on the other side of the orbital process, stabilizing the extracellular matrix and facilitating its expansion, which explains nearly all signs and symptoms of TED.…”

Investigation of the Correlation between Graves’ Ophthalmopathy and CTLA4 Gene Polymorphism

“…We found that those GD-related SNPs were located at different positions in the CTLA4 region within different populations. The majority of patients with GD from different ethnicities were associated with rs231775 and/or rs3087243 (Polish [37,38], Chinese [39,40,41,42,43,44], Saudi Arabian [45,46], Iranian [47,48], Italian [49], Japanese [50], and Taiwanese [17,18,19]). However, rs733618 and its relationship with GO have been found merely in Taiwan population.…”