The Polymorphism rs2968 of LSS Gene Confers Susceptibility to Age-Related Cataract

Research showed that lanosterol can decrease protein aggregation in lens and reduce cataract formation. Lanosterol synthase (LSS) and 3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) are the limiting enzymes in the process of synthesis of lanosterol. We demonstrate to investigate the association between functional single-nucleotide polymorphisms (SNPs) of LSS and HMGCR genes and age-related cataract (ARC) risks in Han Chinese population from Jiangsu Eye Study. This is a case-control study. We collected participants' venous blood for DNA genotyping and lens capsule samples for RNA. The SNPs of the genes were assayed with TaqMan RT-PCR genotyping. The quantitative RT-PCR was used to detect the LSS mRNA levels of lens epithelial cells (LECs) in individuals. The chi-square test was used to compare differences between ARC groups and controls of each SNP and to calculate the odds ratio (OR). We found that LSS-rs2968 of ARCs was different from controls (p = 0.018), but the significance was lost after Bonferroni correction (p = 0.072). We then further performed stratification analysis and found that LSS-rs2968 A allele was associated with nuclear type of ARC risk in Chinese population (p = 0.012, OR = 0.68). Consequently, we found that the mRNA expression of LSS was lower in LECs of all subtypes of ARC group than that of control group (p < 0.05). LSS-rs2968 A allele might play a role in the formation and development of nuclear type of ARC risk in Chinese population.