Polymorphism of the APEX nuclease 1 gene in keratoconus and Fuchs endothelial corneal dystrophy

: Human APEX nuclease 1 (APEX1) plays an important role in the repair of oxidative DNA lesions through base excision repair. It may influence the development of oxidative stress-related diseases. The aim of this study was to determine the relationship between the genotypes of the c.444 T>G (rs1130409) and c.-468 T>G (rs1760944) polymorphisms in the APEX1 gene and the occurrence of two oxidative stress-related eye diseases: keratoconus (KC) and Fuchs endothelial corneal dystrophy (FECD). The study involved 250 patients with KC, 209 patients with FECD, and 350 control subjects. All of the patients and control subjects underwent a detailed ophthalmic examination. The polymorphisms were genotyped by mismatch polymerase chain reaction restriction fragment length polymorphism (mismatch PCR-RFLP). We observed that the G/T and T/T genotypes of the c.-468 T>G polymorphism were respectively associated with a decreased occurrence of KC (OR 0.54, 95% CI 0.37-0.95; p = 0.030) and an increased occurrence of KC (OR 1.87, 95% CI 1.06-3.32; p = 0.032). None of these polymorphisms showed any association with FECD. Furthermore, no other association was observed, including haplotypes of the two polymorphisms. Our findings suggest that the c.-468 T>G polymorphism of the APEX1 gene may play a role in the pathogenesis of KC.