This study evaluated whether variations in the CD103 gene in patients with Graves' disease were associated with the development of Graves' orbitopathy (GO). The authors genotyped multiple CD103 single nucleotide polymorphisms (SNPs) from Chinese Graves' disease patients in Taiwan, some of whom had GO. They found that one of these SNPs-the presence of the G allele at rs11652878, especially Ht5-GCGCG-was more common in GO patients without orbitopathy, which suggests that this variant may be protective against GO. They also investigated nongenetic factors, finding that the development of GO may be associated with age, gender, smoking status, radioiodine treatment and myxedema.
The study included 484 Graves' disease patients, 203 of whom had GO. Using an assay-on-demand allelic discrimination assay and detection system, they genotyped five SNPs (SNP rs1716, rs3744679, rs11652878, rs16953477 and rs9905739) in CD103.
The results indicate that the presence of CD103 SNP rs11652878 may decrease the risk of orbitopathy 1.57 fold (P = 0.029). The authors also found that the Ht5-GCGCG haplotype was more common among patients without GO and may decrease the risk of orbitopathy 1.94 fold. The heterozygous genotype (Ht5/non-Ht5) was more common in patients without orbitopathy, reducing the risk of GO 1.96 fold.
The results provide evidence for the role of polymorphisms in CD103 in the development of GO. This is the first demonstration that the representation of the G allele of SNP rs11652878, especially the Ht5-GCGCG haplotype and heterozygous genotype Ht5/non-Ht5 of CD103, may be associated with protection against the development of GO in Graves' disease patients. Initial activation of T cells in GO is thought to be mediated by several thyroid-related factors, such as the thyrotropin receptor antigen. The authors say that CD103, not only in T cells, may play a crucial role in this eye disease by activating E-cadherin in dermal fibroblasts.
Despite these results, the study had some weaknesses. The authors did not investigate among the normal Taiwanese Chinese population expression of the CD103 gene, which may be similar to one of the groups in the study. They did not specify the characteristics of the control group of Graves' patients without orbitopathy or the way in which these patients were selected. We do not know if they matched the patients with orbitopathy in age, gender, socioeconomic status or habits, such as smoking, or if they suffered from other autoimmune disorders. The authors did not address the possibility that confounding factors were the cause of differences between the groups. Furthermore, the CD103 gene has a causative role in type 1 diabetes mellitus and celiac disease, while, according to this study, it may have a protective role in the development of orbitopathy. Therefore, the study's conclusions regarding this gene should be interpreted with caution.