Exploring the link between Co-stimulatory gene polymorphisms and clinical manifestations in Graves' ophthalmopathy

Graves' ophthalmopathy (GO) is an autoimmune disorder that affects orbital tissues in approximately 30 % of Graves' disease patients. Single nucleotide polymorphisms (SNPs), particularly in immune-related genes, play a crucial role in the development of GO. This study investigates the association between SNPs in co-stimulatory molecules and specific clinical characteristics of GO, including laterality, orbital pain, swelling, diplopia, exophthalmos, redness, and eyelid retraction. Forty-one patients newly diagnosed with GO were analyzed. Genomic DNA was extracted from their blood, and 98 SNPs were amplified using PCR and sequenced. Candidate SNPs, selected based on prior research, were analyzed using chi-square tests and genetic models to assess genotype and allele frequency differences related to clinical manifestations. CD28 SNPs rs3181096 (C vs. T: p = 0.001) and rs3181098 (G vs. A: p = 0.002) were found to show protective effects against eyelid inflammation, while the A-allele of rs200353921(p = 0.005) increased the risk of eyelid inflammation. PDCD1 SNPs rs36084323 (C vs. T: p = 0.004) and rs41386349 (G vs. A: p = 0.005) were linked to diplopia and eyelid inflammation, respectively. The T-allele of rs6705653 in PDCD1 was found to increase the risk of diplopia (p = 0.001) but decreased the risk of eyelid retraction (p = 0.002). Other SNPs, including rs2227982 (p = 0.003) and rs2227981 (G vs. A: p = 0.001), were also associated with diplopia and eyelid retraction, highlighting the complex genetic influences on the clinical manifestations of GO. Furthermore, interactions between age, gender, and SNPs were observed in relation to GO clinical features. These findings highlight the potential regulatory roles of these genes in influencing immune responses and orbital inflammation in GO. Understanding these genetic influences could help identify predictive markers and novel therapeutic targets for GO management.