Interleukin-13 gene polymorphisms in patients with Graves' disease

Abstract

Objective: In patients with Graves' disease (GD), an elevation of serum immunoglobulin E (IgE) has been recently reported to be associated with the severity of hyperthyroidism and ophthalmopathy. Interleukin 13 (IL-13) is a major cytokine involved in IgE synthesis and therefore may be a potential candidate gene contributing to the development of GD or influencing the clinical course of the disease.

Design: In a case-control study, we examined IL-13 gene single-nucleotide polymorphisms in the 5' promoter region at position -1112 (C to T change, termed as C-1112T) and in exon 4 at position 2044 (G to A change, G2044A, which results in an amino acid exchange Arg130Gln) in 261 patients with GD. The control groups consisted of healthy young subjects (n=168) and subjects over 100 years old with no history of autoimmune or allergic diseases recruited from the Polish Centenarians Project (n=50).

Measurements: C-1112T and G2044A polymorphisms were defined by fluorescent single-strand conformational polymorphism and by restriction fragment length polymorphism analysis, respectively.

Results: In patients with GD, the distribution of IL-13 alleles (-1112T 31%; 2044A 25%) and genotypes (-1112T/T 10%; 2044A/A 7%) did not differ significantly compared to control groups. Subdividing GD patients according to clinically evident ophthalmopathy (NOSPECS class III or higher, n=93) revealed no significant differences in the frequencies of -1112T allele (33%vs. 29%; P=0.4), -1112T/T genotype (13%vs. 8%; P=0.3), 2044A allele (27%vs. 24%; P=0.5) and 2044A/A genotype (9%vs. 7%; P=0.7) between GD patients with and without eye involvement. In order to analyse the association with the severity of hyperthyroidism, we examined patients with a first onset of GD treated with antithyroid drugs (n=32). IL-13 genotypes were not associated with the laboratory findings at diagnosis (thyroid volume, serum levels of FT4, TRAb, TPOAb, TGAb) and with the outcome of antithyroid drug treatment.

Conclusions: Our results suggest that IL-13 gene polymorphisms at positions -1112 (C-->T) and 2044 (G-->A): (1) do not confer genetic susceptibility to Graves' disease; (2) do not contribute to the development of clinically evident ophthalmopathy; (3) are not associated with severity of hyperthyroidism.