Jwu Jin Khong
Purpose: We aimed to determine differentially expressed genes in thyroid orbitopathy (TO) using microarray gene profiling in a case-control study.
Methods: RNA from Human orbital adipose samples in individuals with active TO (n=12), inactive TO (n=21) and normal controls (n=21) were subjected to microarray analysis. Gene expression was compared between active and inactive TO, and between active TO and normal controls. Top ranked genes were validated by real-time RT-PCR and correlated with gene set enrichment analysis and molecular pathways analysis.
Results: 721 probes representing 683 annotated genes were significantly differentially expressed in active compared to inactive TO. Fifteen of 17 differentially expressed genes were validated by real time RT-PCR. Defensins (DEFA1, DEFA1B, DEFA3) were overexpressed by 3.05-4.14-fold. TIMD4 was over-expressed by 4.3-fold. CD247, CAMP, SLAMF6, GZMA, NKG7, EOMES, CCL5 were upregulated by 1.74-1.95 fold. Markers for adipogenesis were over-expressed by 1.91-2.6 fold including SCD, FADS1 and ELOVL6. Increased expression of FADS1, SCD and SREBF1 was also confirmed in active TO versus normal controls.
Conclusions: Active TO is marked by up-regulation of genes involved in the cellular, innate immune and inflammatory response and enhanced orbital adipogenesis. TIMD4, DEFA1, DEFA1B and DEFA3 may be involved in the innate immune-mediated orbital inflammation in thyroid orbitopathy.