Background: Environmental and genetic factors predispose an individual to the development of Graves' disease (GD). In an expression study of intraorbital tissue, adipocyte-related immediate early genes (IEGs) and immunomodulatory genes were found to be overexpressed in patients with Graves' ophthalmopathy (GO). We hypothesized that genetic variations in these genes could be associated with GD and/or GO.
Methods: A total of 98 single nucleotide polymorphisms (SNPs) in 12 genes were genotyped in 594 GD patients with (n=267) or without (n=327) GO and 1147 sex- and ethnicity-matched controls from Malmö, Sweden.
Results: Ten SNPs in four genes (BTG family, member 2 [BTG2], cysteine-rich, angiogenic inducer 61 [CYR61], zinc finger protein 36, C3H type, homolog mouse [ZFP36], and stearoyl-coenzyme A desaturase [SCD]) showed an association with GD and/or GO. SNPs rs12136280 (odds ratio [OR] 1.29, p=0.002), rs6663606 (OR 1.26, p=0.004), and rs17534202 (OR 1.21, p=0.02) in BTG2 and rs3753793 (OR 1.21, p=0.03) in CYR61 were associated with GD. An association with GO was shown for SNPs rs3753793 (OR 1.45, p=0.008), rs6682848 (OR 1.55, p=0.03), rs12756618 (OR 1.77, p=0.049), and rs1378228 (OR 1.29, p=0.049) in CYR61, rs1057745 (OR 1.56, p=0.03) and rs11083522 (OR 1.32, p=0.04) in ZFP36, and rs1393491 (OR 1.38, p=0,048) in SCD. Smoking and CYR61 rs12756618 interacted to increase the risk of GO.
Conclusions: We found associations of SNPs in IEGs and SCD with GD and/or GO; however, confirmation in a different population is required.