| Purpose:DNA damage is critical in the pathogenesis of age-related cataract (ARC). CNVs is important genetic basis of human genetic variation. This study was to examine the association of copy number variations (CNVs) of DNA repair genes with susceptibility to ARC in the Han Chinese.Methods:Study participants were from a population-based "Jiangsu Eye Study", including780ARC patients (including257cortical,368nuclear,34posterior subcapsular and121mixed type of ARC) and525controls. DNA was extracted from blood for copy number (CN) assays using RT-PCR. The odds ratios (OR) and95%confidence intervals (CI) were calculated to estimate the genotype distributions of CNVs between ARC patients and normal controls. The Comet assay was to assess DNA damage in peripheral lymphocytes.Results:Novel CNV was detected in WRN. Initial analyses found that CN=3+for WRN had an increased risk of ARC (OR=1.88, P=0.02); CN=1for HSF4had an increased risk of ARC (OR=4.09, P=0.004). After Bonferroni correction, HSF4CNV is associated with ARC as before.CN=3+for WRN was associated with nuclear and posterior subcapsular cataract (OR=2.06, P=0.02; and OR=3.72, P=0.02). CN=1for HSF4was associated with nuclear and posterior subcapsular cataract (OR=5.73, P=0.001; and OR=6.80, P=0.01). After Bonferroni correction, HSF4CNV is associated with nuclear and posterior subcapsular cataract as before.The combination WRN and HSF4CNVs markedly increased the risk of ARC, the OR was increased from2.63by HSF4alone to6.80by combined WRN and HSF4CNVs. However, after Bonferroni correction, there was no statistically significant difference.The DNA damage in lymphocytes from ARC patients was significantly higher when compared to normal controls. And in the male group and female group, the DNA damage in peripheral blood lymphocyte were higher than control group, difference has statistical significance (p<0.01).Conclusions:HSF4and 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. |
