Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2014) 35 P986 | DOI: 10.1530/endoabs.35.P986

ECE2014 Poster Presentations Thyroid (non-cancer) (125 abstracts)

Polymorphisms within genes encoding co-stimulatory molecules modulate the susceptibility to Graves' disease and orbitopathy

Jacek Daroszewski 1 , Edyta Pawlak-Adamska 2 , Janusz Przemyslaw 1 , Irena Frydecka 2 , Lidia Karabon 2 , Anna Jonkisz 2 , Anna Tomkiewicz 2 , Anna Partyka 2 , Arleta Lebioda 3 & Marek Bolanowski 1

1Department of Endocrinology, Diabetes and Isotope Therapy, Wroclaw Medical University, Wroclaw, Poland; 2Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland; 3Department of Forensic Medicine, Wroclaw Medical University, Wroclaw, Poland.

The clinical presentation of Graves’ disease (GD) depends on the combination of environmental and genetic factors. The CTLA-4 and CD28, ICOS genes encoding negative and positive regulator of the T-lymphocyte immune response, are candidate genes for conferring susceptibility to thyroid autoimmunity.

Polymorphisms in genes: CTLA-4: g.319C>T (rs5742909), c.49A>G (rs231775), g.*642AT(8_33), CT60 (g.*6230G>A, rs3087243), Jo31 (g.*10223G>T, rs11571302), CD28: c.17+3T>C (rs3116496) and ICOS: c.1554_4GT(8_15) were determined in 172 GD patients and 381 healthy persons. Data were analyzed in the context of familial history of thyroid disease, response to the anti-thyroid treatment and severity of Graves’ orbitopathy (GO).

Carriers of G allele in marker CT60 (genotype GG and/or GA) had increased risk of GD 1.80 (P=0.04, OR=1.80, 95%CI: 1.03–3.14). Carriers of alleles with 12–21 AT repeat at g.*642AT (8_33) were 1.84-more prone to the disease (P=0.001, 95%CI: 1.26–2.69). The multivariate logistic regression analysis showed that only g.*642AT (8_33) marker is an independent risk factor for disease (χ2=33.3, P=0.0008). Moreover, CT60G allele and presence of G allele significantly reduced the rate of a successful medical anti-thyroid treatment (P=0.002, and P=0.01 respectively). Similar results were observed for marker Jo31. The multivariate logistic regression analysis showed that only the CT60 marker is an independent risk factor of the progression of GD (χ2=114.6, P=0.009). We also observed that carriers of CTLA-4g.319C>T CC genotype were over-represented in a subgroup with familial history of thyroid disease (81.2% vs 47.1%, P=0.00005). Carriers of c.49A>G G allele more often develop severe GO (P=0.02, OR=2.17, 95%CI:1.10–4.30). Moreover, patients carrying allele of 12–21 AT repeat at g.*642AT(8_33) more often develop severe GO (P=0.01, 95%CI: 1.19–4.53). The multivariate logistic regression analysis pointed that g.*642AT (8_33) marker as well as male gender are independent risk factor for GO (P=0.04, and P=0.00008 respectively).

Our results suggest that polymorphisms within gene encoding the CTLA-4 molecule influence the risk of GD and modifies the clinical course of the disease.

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