title: Copy number variations of DNA repair genes and the age-related cataract: Jiangsu Eye Study.
abstract: OBJECTIVE
  DNA damage is critical in the pathogenesis of age-related 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 = 3+ for WRN had an increased risk of ARC (odds ratio [OR] = 1.88, P = 0.02); CN = 1 for HSF4 had an increased risk of ARC (OR = 4.09, P = 0.004). CN = 3+ for WRN was associated with nuclear and posterior subcapsular cataract (OR = 2.06, P = 0.02; OR = 3.72, P = 0.02). CN = 1 for HSF4 was associated with nuclear and posterior subcapsular cataract (OR = 5.73, P = 0.001; OR = 6.80, P = 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.
authors: Eye Institute, Affiliated Hospital of Nantong University, Jiangsu Province, China.
authors: Jin
authors: J
authors: Jiang
authors: Jing
authors: J
authors: Zhou
authors: Yong
authors: Y
authors: Yao
authors: Rongrong
authors: R
authors: Zhu
authors: Congkai
authors: C
authors: Liang
authors: Shengqun
authors: S
authors: Jiang
authors: Mei
authors: M
authors: Yang
authors: Yixiang
authors: Y
authors: Lu
authors: Qian
authors: Q
authors: Xing
authors: Huaijin
authors: H
authors: Guan
mesh_terms: D000368:Aged; D000375:Aging / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D002386:Cataract / Q000453:epidemiology / Q000235:genetics*; D002681:China / Q000453:epidemiology; D020552:Comet Assay; D004247:DNA / Q000235:genetics*; D056915:DNA Copy Number Variations; D004268:DNA-Binding Proteins / Q000235:genetics*; D005090:Exodeoxyribonucleases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D000076249:Heat Shock Transcription Factors; D006801:Humans; D008297:Male; D016017:Odds Ratio; D053484:RecQ Helicases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*; D000071657:Werner Syndrome Helicase
chemical_list: D004268:DNA-Binding Proteins; C102948:HSF4 protein, human; D000076249:Heat Shock Transcription Factors; D014157:Transcription Factors; D004247:DNA; D005090:Exodeoxyribonucleases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase