Eye Institute, Affiliated Hospital of Nantong University, Jiangsu Province, China.
Invest Ophthalmol Vis Sci. 2013 Feb 1;54(2):932-8. doi: 10.1167/iovs.12-10948.
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.
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.
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.
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.
DNA 损伤在年龄相关性白内障（ARC）的发病机制中至关重要。本研究探讨了 DNA 修复基因的拷贝数变异（CNV）与汉族人群 ARC 易感性的关系。
研究对象来自基于人群的江苏眼病研究，其中包括 780 例 ARC 患者和 525 例对照。从血液中提取 DNA 进行 RT-PCR 拷贝数（CN）检测。彗星试验评估外周血淋巴细胞的 DNA 损伤。
在 WRN 中检测到新的 CNV。初步分析发现，WRN 的 CN = 3+ 增加了 ARC 的风险（优势比[OR] = 1.88，P = 0.02）；HSF4 的 CN = 1 增加了 ARC 的风险（OR = 4.09，P = 0.004）。WRN 的 CN = 3+ 与核性和后囊下白内障相关（OR = 2.06，P = 0.02；OR = 3.72，P = 0.02）。HSF4 的 CN = 1 与核性和后囊下白内障相关（OR = 5.73，P = 0.001；OR = 6.80，P = 0.01）。WRN 和 HSF4 的 CNV 联合显著增加了 ARC 的风险；OR 由 HSF4 单独的 2.63 增加到 WRN 和 HSF4 的联合 CNV 的 6.80。然而，经过多次测试校正后，只有 HSF4 的 CNV 与 ARC 总体以及核性和后囊下白内障有关。与正常对照组相比，ARC 患者的淋巴细胞 DNA 损伤明显更高。
HSF4 和 WRN 的 CNV 可能参与了汉族人群 ARC 的发病机制。这些发现表明 DNA 修复在 ARC 易感性和不同 ARC 亚型的危险因素中具有重要作用。
