Ming-Ming Yang, Li Dong, Dian-Jun Sun, Yan Teng, Ping Liu
Genetic Investigation of Ocular Inflammatory Diseases
Uveitis is a group of heterogeneous ocular inflammatory diseases with complex phenotypes, which causes substantial visual impairment and accounts for about 10% of blindness worldwide among the working age group.
Based on our understanding of the critical checkpoints in the uveitis process, two major pathways, T-cell response and complement system, appear to be most related to uveitis in the molecular level. We therefore target on several molecular factors involved in the pathway to evaluate the genetic impact on susceptibility to uveitis.
A series of candidate gene association studies were performed with involvement of more than 500 uveitis patients, clinical information and demographic conditions of the patients were documented. We also conducted interaction analysis to reveal the putative clinical markers for uveitis. Genotype-phenotype correlations were performed to explore their relationships with the disease severity and progression.
Collectively, our results provide evidence for the involvement of the complement system in the disease pathogenesis of uveitis. CFH and CFB, involved in the alternative pathway, are identified as genetic risk factors for uveitis. Other complement pathway genes, SERPING1 (C1INH), C3 and C5, as well as IL2_21 region and IL27 involving in the T-cell response, confer either no or limited risk for the development of uveitis.
Future genetic and immunologic investigations in uveitis and other ocular inflammatory diseases should therefore be focused on the complement system and the alternative pathway.
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