The associations between single nucleotide polymorphisms of DNA repair genes, DNA damage, and age-related cataract: Jiangsu Eye Study

Abstract

Purpose: Age-related cataract (ARC) is one of the most common causes of severe visual impairment among the elderly worldwide with four subtypes, such as cortical, nuclear, subcapsular, and mixed types. DNA damage and malfunction of DNA repair are believed to contribute to the pathogenesis of ARC. This study examined the associations of 18 single nucleotide polymorphisms (SNPs) in four DNA repair genes (BLM, WRN, ERCC6, and OGG1) with ARC in Han Chinese from the Jiangsu Eye Study, a population-based epidemiologic study. We also determined the possible functional consequence of the SNPs to DNA damage.

Methods: Eighteen SNPs in four DNA repair genes were genotyped in 789 ARC patients and 531 normal controls from the Jiangsu Eye Study. The Comet assay was to assess the extent of DNA damage in peripheral lymphocytes of selected subjects.

Results: The results show that WRN-rs11574311 was initially associated with ARC in general, cortical, and mixed cataracts (P = 0.003, odds ratio [OR] = 1.49; P = 0.001, OR = 1.68; and P < 0.0001, OR = 2.08), BLM-rs1063147 with nuclear cataract (P = 0.03, OR = 1.31), WRN-rs2725383 with cortical cataract (P = 0.01, OR = 1.49), and WRN-rs4733220 and WRN-rs2725338 with mixed cataract (P = 0.04, OR = 0.74; P = 0.003, OR = 0.60). However, the significances of some of the above-cited associations disappeared after multiple testing corrections. WRN-rs11574311 remains associated with cortical and mixed cataract and WRN-rs2725338 with mixed cataract after multiple testing correction. We did not find any correlation between DNA damage of peripheral lymphocytes and SNP types.

Conclusions: We concluded that WRN genes might be involved in ARC pathogenesis in the 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.