The signaling pathway of IL-6 has been reported to be associated with the severity of glaucoma. And the rs12976445 SNP in miR-125 could alter the expression of miR-125, which is directly targeted by IL-6R.

Material and methods:
In this study, we recruited 88 POAG patients and grouped them according to their genotype of rs12976445 as GG group, GC group and CC group to study the association between the miR-125a polymorphism and POAG. We collected demographic characteristics and peripheral blood samples from 88 subjects. Then, rs12976445 genotypes in these subjects were determined to evaluate their relationship with the POAG index. THP-1 and U937 cells were transfected with miR-125a mimic or IL-6R siRNA to assess the relationship between miR-125a and IL-6R/ACHE.

IL-6R is a downstream target of miR-125a and the overexpression of miR-125a showed significantly decreased mRNA and protein levels of IL-6R. The expression levels of miR-125a were the highest in the GG group and the lowest in the CC group, while the activity of IL-6 was comparable in the three groups. Moreover, the mRNA and protein levels of IL-6R were the lowest in the GG group and the highest in the CC group. Additionally, significantly thinner RNFL, larger average cup disc ratio, larger vertical cup disc ratio, and depressed visual field were observed in POAG patients carrying the CC genotype.

In summary, our data suggested that the rs12976445 polymorphism was significantly associated with the risk of POAG.