Association of polymorphisms in the intron of TCF4 gene to late-onset Fuchs endothelial corneal dystrophy: An Indian cohort study

PURPOSE Fuchs endothelial corneal dystrophy (FECD) is a progressive degenerative disease of the corneal endothelium. It is genetically heterogeneous and follows either an autosomal dominant or sporadic pattern of inheritance. Here, we have explored the association of four previously reported intronic single nucleotide polymorphisms and intronic CTG repeat expansions in TCF4 gene to FECD in an Indian cohort. METHODS The cohort consisting of 52 sporadic late-onset cases, 5 early-onset cases, and 148 controls was taken for the study. rs2286812 and rs613872 were genotyped by allele specific polymerase chain reaction (ASPCR) and PCR-based restriction digestion, respectively; rs17595731 and rs9954153 were genotyped by Taqman assay using real-time PCR. The quantitative assessment of the CTG repeat region was performed by PCR/Sanger DNA sequencing. The repeats were assessed qualitatively by short tandem repeat and triplet repeat primed PCR assays. The statistical analysis was performed using two-tailed Fisher's exact probability test. RESULTS SNPsrs613872 (G/T) for the 'G' allele (P value: 4.57 × 10-5) and rs17595731 (C/T) for the 'C' allele (P value: 1.87 × 10-5), respectively, showed a significant association to sporadic late-onset FECD. CTG repeat expansions were found to be associated with FECD with a P value = 2.4 × 10-3. CONCLUSION rs613872, rs17595731, and CTG repeat expansions in intronic region of TCF4 are associated with increased risk of sporadic late-onset FECD in the Indian cohort studied.