Abstract
This study was to explore the involvement of DNA repair genes in the pathogenesis of age-related cataract (ARC). We genotyped nine single nucleotide polymorphisms (SNPs) of genes responsible to DNA double strand breaks (DSBs) in 804 ARC cases and 804 controls in a cohort of eye diseases in Chinese population and found that the ataxia telangiectasia mutated (ATM) gene-rs4585:G>T was significantly associated with ARC risk. An in vitro functional test found that miR-2964a-5p specifically down-regulated luciferase reporter expression and ATM expression in the cell lines transfected with rs4585 T allele compared to rs4585 G allele. The molecular assay on human tissue samples discovered that ATM expression was down-regulated in majority of ARC tissues and correlated with ATM genotypes. In addition, the Comet assay of cellular DNA damage of peripheral lymphocytes indicated that individuals carrying the G allele (GG/GT) of ATM-rs4585 had lower DNA breaks compared to individuals with TT genotype. These findings suggested that the SNP rs4585 in ATM might affect ARC risk through modulating the regulatory affinity of miR-2964a-5p. The reduced DSBs repair might be involved in ARC pathogenesis.
Highlights
Age-related cataract (ARC) is a progressive opacification of the ocular lens which can lead to visual impairment and blindness
We compared the allele frequency between age-related cataract (ARC) patients and normal controls and found that only ataxia telangiectasia mutated (ATM)-rs4585 was associated with ARC (P=0.0022, odds ratios (OR)=1.24, 95% confidence interval (CI): 1.06–1.40; Table 3 ), and the significance remained after Bonferroni correction (Pa =0.0198)
It has been demonstrated that the aberrant overexpression of miR-421 may down-regulated ATM, can lead to SKX squamous cell carcinoma [35].In addition, it has been shown that miR-203 may be responsible for ATM down-regulation in breast cancers [12]
Summary
Age-related cataract (ARC) is a progressive opacification of the ocular lens which can lead to visual impairment and blindness. Based on the opacity location within the lens, ARC can be classified into the following subtypes: cortical cataract (C), nuclear cataract (N), posterior subcapsular cataract (PSC) and mixed cataract (M)[1]. ARC is a multifactorial disease caused by the interactions between genes and environmental factors. Various risk factors like aging, diabetes, gender, sunlight radiation and UV exposure have been associated with cataract development and progression [2]. It is known that external factors such as ionizing radiation and certain chemotherapeutic drugs can generate oxidative stress and induce damages of DNA within the lens epithelium. Disrupted DNA repair genes, which could be caused by gene variation, have been reported to be strongly associated with ARC [3, 4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
