Association of Common Variants in TCF4 and PTPRG with Fuchs' Corneal Dystrophy: A Systematic Review and Meta-Analysis

TOPIC A meta-analysis of TCF4 and PTPRG gene variants in Fuchs' corneal dystrophy (FCD). CLINICAL RELEVANCE To identify novel genetic markers in patients with FCD in different ethnic populations. METHODS MEDLINE and EMBASE were searched for eligible genetic studies on TCF4 and PTPRG in FCD. Odds ratios (OR) and 95% confidence intervals (CI) of each single-nucleotide polymorphism (SNP) in allelic, dominant and recessive models were estimated using fixed-effect model if I2<50% in the test for heterogeneity, otherwise the random effects model was used. RESULTS Thirty-three records were obtained, with 8 being suitable for meta-analysis, which included five SNPs in TCF4 and two in PTPRG. There were 1610 FCD patients and 1565 controls tested for TCF4 rs613872. This SNP was strongly associated with FCD in Caucasians (P = 5.0×10-106), with the risk allele G conferring an OR of 3.95 (95% CI: 3.49-4.46). A further 4 TCF4 SNPs (rs17595731, rs2286812, rs618869 and rs9954153) were also significantly associated with FCD in Caucasians (P<10-8). However, we found no SNP associated with FCD in Chinese. In addition, there was no significant association between FCD and PTPRG. CONCLUSION TCF4 rs613872 is strongly associated with FCD in Caucasians but not in Chinese, which may suggest ethnic diversity in FCD SNP associations. SNPs in PTPRG were not associated with FCD in Caucasians or Chinese populations. Results of this meta-analysis indicate the need for larger-scale and multi-ethnic genetic studies on FCD to further explore the associated gene variants and their roles on the mechanism and genetic basis of FCD.