Copy Number Variations of DNA Repair Genes and the Age-Related Cataract: Jiangsu Eye Study

Abstract

PURPOSE. DNA damage is critical in the pathogenesis of agerelated cataract (ARC). This study examined the association of copy number variations (CNVs) of DNA repair genes with susceptibility to ARC in the Han Chinese.METHODS. Study participants were from the population-based Jiangsu Eye Study, which includes 780 ARC patients and 525 controls. DNA was extracted from blood for copy number (CN) assays using RT-PCR. The Comet assay was to assess DNA damage in peripheral lymphocytes. RESULTS.Novel CNV was detected in WRN. Initial analyses found that CN ¼ 3þ for WRN had an increased risk of ARC (odds ratio [OR] ¼ 1.88, P ¼ 0.02); CN ¼ 1 for HSF4 had an increased risk of ARC (OR ¼ 4.09, P ¼ 0.004). CN ¼ 3þ for WRN was associated with nuclear and posterior subcapsular cataract (OR ¼ 2.06, P ¼ 0.02; OR ¼ 3.72, P ¼ 0.02). CN ¼ 1 for HSF4 was associated with nuclear and posterior subcapsular cataract (OR ¼ 5.73, P ¼ 0.001; OR ¼ 6.80, P ¼ 0.01). The combination WRN and HSF4 CNVs markedly increased the risk of ARC; the OR was increased from 2.63 by HSF4 alone to 6.80 by combined WRN and HSF4 CNVs. However, after multiple testing correction, only HSF4 CNV was associated with ARC overall and with nuclear and posterior subcapsular cataract as well. The DNA damage in lymphocytes from ARC patients was significantly higher when compared to normal controls.CONCLUSIONS. HSF4 and WRN CNVs might be involved in ARC pathogenesis in the Han Chinese. These findings suggest the importance of DNA repair in ARC susceptibility and distinct risk factors in ARC subtypes. (Invest Ophthalmol Vis Sci. 2013; 54:932-938)

Effects of combined physical exercise training on DNA damage and repair capacity: role of oxidative stress changes

“…The decrease in oxidative damage associated with exercise training could be explained by an increase in antioxidant and metabolic efficiency, which possibly prevent the stimulation of DNA repair enzyme activity. These results enhance the importance of regular exercise in the prevention of DNA damage accumulation which has been related to aging (Nalapareddy et al 2008) and some agerelated diseases including: cardiovascular disease (Collins et al 1998), diabetes mellitus (HannonFletcher et al 2000), cataracts (Jiang et al 2013;Su et al 2013), and several cancers (Malins et al 2001;Akcay et al 2003;Peddireddy et al 2012). In addition, it should be noted that DNA damage depends on a complex system which is not thoroughly understood.…”

Altered DNA Methylation and Expression Profiles of 8-Oxoguanine DNA Glycosylase 1 in Lens Tissue from Age-related Cataract Patients

“…13 Previously, we reported that polymorphisms and copy number variations of some DNA repair genes, such as Werner syndrome protein (WRN), are involved in ARC pathogenesis, but two SNPs in OGG1 (rs2072668 and rs2304277) were not associated with an increased risk of ARC. 14,15 DNA methylation is an important epigenetic mechanism in gene regulation and is usually associated with transcriptional silencing of genes without alteration of the DNA sequence. Methylation at the C5 position of cytosine is a common epigenetic modification, and cytosine methylation in CpG dinucleotides can occur.…”

DNA Damage in Lens Epithelial Cells and Peripheral Lymphocytes from Age-Related Cataract Patients

“…Our previous studies have detected DNA damage of peripheral lymphocytes by comet assay in ARC patients from a population-based study. We found that DNA damage of peripheral lymphocytes was significantly higher in ARC patients and associated with DNA repair gene polymorphisms [11,13,14]. …”