Ubiquitin Carboxyl-Terminal Esterase LI (UCHLI) SI8Y Polymorphism in Patients with Cataracts

BACKGROUND  Cataract is characterized by light-scattering protein aggregates. The ubiquitin-proteasome system has been proposed a role in proteolytic removal of these protein aggregates. Ubiquitin carboxyl-terminal esterase L1 (UCHL1) is a de-ubiquitinating enzyme with important functions in recycling of ubiquitin. A protective role of the p.S18Y polymorphism of the UCHL1 gene has been shown in Parkinson`s disease. The current study aimed to examine possible effects on cataract formation. METHODS  Patients with cataract (n = 493) and controls (n = 142) were analyzed for the UCHL1 p.S18Y polymorphism using dynamic allele-specific hybridization. RESULTS  Significant differences were observed in allele and genotype frequencies of the p.S18Y polymorphism between controls and cataract patients, where a positive UCHL1 allele A carrier status was associated with the cataract diagnosis (adjusted OR 1.7 [95% CI = 1.1-2.6] p = 0.02). No significant differences were seen in genotype distribution when stratifying for type of cataract. Nor did the mean age at cataract surgery differ between genotypes. CONCLUSION  The current study does not support a protective role for the UCHL1 S18Y polymorphism in cataract development, but may instead suggest a disease-promoting effect.