Characterisation of the role played by ELMO1, GPR141 and the intergenic polymorphism rs918980 in Fuchs' dystrophy in...

Fuchs' endothelial corneal dystrophy (FECD) is the most common type of primary corneal dystrophy and can result in corneal transplantation. Here, we investigated the genetic association of SNP rs918980 (A>G) with FECD and the role of its surrounding genes ELMO1 and GPR141. First, 128 patients and 379 controls were genotyped by Sanger sequencing. Our results show that rs918980 is significantly associated with FECD in the Indian population. Furthermore, in silico analysis suggested that rs918980 and its surrounding 150 bp region could regulate the transcriptional activities of nearby genes. Thus, we assessed whether ELMO1 and GPR141 were differentially expressed in FECD patients and in the corneal tissue of a UVA-induced FECD mice model. Both genes were significantly upregulated and western blots studies concluded that protein levels of ELMO1 and GPR141 were also higher in the corneal endothelium of the UVA-exposed eye compared to the control eye. Taken together, our results suggest that ELMO1 and GPR141 might play a significant role in FECD progression. However, further studies are required to better characterize the possible role of rs918980 and its nearby region in the regulation of ELMO1 and GPR141.