Genetic Variants of Interleukin 17A Are Functionally Associated with Increased Risk of Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in elderly populations worldwide. Inflammation, among many factors, has been suggested to play an important role in AMD pathogenesis. Interleukin 17 (IL-17) is a proinflammatory cytokine that has been implicated in the pathogenesis of various autoimmune diseases. In the current study, we examined two single nucleotide polymorphisms (SNPs), rs2275913G/A and rs3748067C/T, in the IL-17A gene between AMD patients and healthy controls. Results showed that rs2275913AA genotype and rs3748067TT genotype were associated with increased susceptibility to AMD (hazard ratio [HR], 1.75; 95 % confidence interval [CI], 1.07 to 3.02; P = 0.023, and HR, 2.12; 95 % CI, 1.26 to 4.01; P = 0.004; data were adjusted for age and sex). Next, we investigated the functional relevance of the two SNPs. In vitro stimulated peripheral blood mononuclear cells (PBMCs) from subjects possessing the rs2275913AA genotype produced significantly more IL-17 than those with the GG genotype. However, PBMCs with rs3748067TT genotype revealed significantly higher IL-17 production than those with rs3748067CC genotype only in AMD patients but not in controls. These data indicate IL-17A polymorphisms are associated with increased risk of AMD probably by affecting gene expression. [ABSTRACT FROM AUTHOR]

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