Intergenic variants, rs1200114 and rs1200108 are genetically associated along with a decreased ATP1B1 expression in Fuchs Endothelial Corneal Dystrophy

Exp Eye Res. 2023 Mar:228:109403. doi: 10.1016/j.exer.2023.109403. Epub 2023 Feb 1.


Fuchs endothelial corneal dystrophy (FECD) is an age-related, bilateral corneal condition, characterized by apoptosis of the terminally differentiated endothelial cells. A genome-wide association study (GWAS) conducted in the European population in 2017, identified a new single nucleotide polymorphism (SNP), rs1200114 in the intergenic region between long intergenic non-protein coding RNA 970 (LINC00970) and ATPase Na+/K+ transporting subunit beta 1 (ATP1B1). The major focus of the current study is to understand the genetic association of this intergenic variant, rs1200114 with FECD in the Indian population. Sanger sequencing followed by statistical analysis indicated a significant difference in the allelic frequency between controls and cases (P = 0.01) with the minor allele 'G' of rs1200114 imparting a 1.64 fold increased risk for the disease. Luciferase reporter assay revealed no significant difference in the luciferase activity between allele 'A' and 'G' of rs1200114. However, quantitative RT-PCR assay revealed lower expression of ATP1B1 in FECD subjects compared with controls (P = 0.007). Therefore, to find whether another nearby SNP imparts regulatory effect, tag SNP association analysis was carried out; which revealed a significant association of another SNP, rs1200108, present in the intergenic region between LINC00970 and ATP1B1 with FECD (P = 0.009). The protective allele 'A' of rs1200108 displayed reduced reporter activity as opposed to the risk allele 'G' (P = 0.014). Furthermore, haplotype 'A-A' of rs1200108 - rs1200114 was present at a higher frequency in control subjects, suggesting it as a protective haplotype. Altogether, this study inferred the genetic association of rs1200114 and rs1200108 along with the decreased expression of ATP1B1 related to FECD pathogenesis in the Indian population.

Keywords: Corneal endothelium; Haplotype; Linkage disequilibrium; Polymorphism; Tag SNP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA, Intergenic
  • Endothelial Cells / pathology
  • Endothelium, Corneal / pathology
  • Fuchs' Endothelial Dystrophy* / genetics
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Sodium-Potassium-Exchanging ATPase / genetics


  • DNA, Intergenic
  • ATP1B1 protein, human
  • Sodium-Potassium-Exchanging ATPase