The Associations Between Single Nucleotide Polymorphisms Of DNA Repair Genes, DNA Damage And Age-related Cataract

Background Age-related cataract (ARC) is one of the most common causes of severe visual impairment among the elderly worldwide. ARC is classified in4subtypes, e.g. cortical, nuclear, subcapsular and mixed types. DNA damage and malfunction of DNA repair are believed to contribute to the pathogenesis of ARC.Purpose This study examined the associations of18single nucleotide polymorphisms (SNPs) in4DNA repair genes (BLM, WRN, ERCC6and OGG1) with ARC in Han Chinese from Jiangsu Eye Study, a population-based epidemiological study. Meanwhile, we determined the functional contribution of the SNP in DNA damage.Methods This study was a part of the Jiangsu Eye Study, a population-based epidemiological study. We examined789ARC patients (C=257, N=366, P=34, M=132), the average age is70.38±7.72in ARC patients. Normal controls were also selected from Binhu District and Funing County. There was no biogenetic relation between normal controls, and between normal controls and ARC patients. After matching for age and gender,531individuals were included as normal controls. Peripheral venous blood was collected in an EDTA anticoagulation tube. Genomic DNA was isolated from leukocytes by phenol-chloroform method. Genotyping of all18SNPs were conducted with Taqman assay. The Chi-square test was used to test the association between the alleles frequencies of all ARC patients and normal controls and various subtypes of ARC, and to estimate odds ratios (OR) and95%confidence interval (CI). The Comet assay was performed on69ARC patients (N=22, C=32, M=15) and28age-and gender-matched normal controls to evaluate the extent of DNA damage (DNA breaks) in individual cells. The ANOVA was used to compare the differences of the Comet assay parameters between the genotypes. P<0.05was considered as statistically significant.Results The results show that WRN-rsl1574311was initially associated with ARC in general, cortical and mixed cataract (P=0.003,OR=1.49; P=0.001, OR=1.68and P<0.0001, OR=2.08), BLM-rs1063147with nuclear cataract (P=0.03, OR=1.31), WRN-rs2725383with cortical cataract (P=0.01, OR=1.49), WRN-rs4733220and WRN-rs2725338with mixed cataract (P=0.04, OR=0.74and P=0.003, OR=0.60). However, the significances of some above association disappeared after multiple testing corrections. However, WRN-rs11574311remains associated with cortical and mixed cataract, WRN-rs2725338with mixed cataract after multiple testing correction. We did not find correlation between DNA damage of peripheral lymphocytes and SNP types.Conclusions We concluded that WRN and BLM genes might be involved in ARC pathogenesis in Han Chinese population. The associations were ARC subtype specific. These findings stress the importance of detailed phenotyping in ARC subtypes, which may be associated with different risk factors and disease mechanisms. There is no correlation of DNA damage of peripheral lymphocytes with the genotypes of the SNPs.