DNA修复基因的拷贝数变异与年龄相关性白内障的关系

目的探讨中国汉族人群中DNA修复基因的拷贝数多态性(copy number variations,CNV)与年龄相关性白内障(age-related cataract,ARC)易感性的关系。方法研究对象来自"江苏眼病研究"流行病学人群,包括ARC组780例和对照组525人。采集受试者外周静脉血,提取全血基因组DNA。通过实时荧光定量PCR方法检测四种DNA修复基因的拷贝数(copy number,CN),分析ARC组和对照组基因CN的差异以及相对危险度(odds ratio,OR)。结果在WRN基因中发现了新的CNV。WRN基因高拷贝(CN=3+)与ARC的易感性有关(OR=1.88,P=0.02);HSF4基因低拷贝(CN=1)的人群对ARC易感(OR=4.09,P=0.004)。WRN基因高拷贝与核性以及后囊下性ARC的易感性有关(OR=2.06、3.72,均为P=0.02)。HSF4基因低拷贝与核性以及后囊下性ARC的易感性有关(OR=5.73,P=0.001;OR=6.80,P=0.01)。WRN和HSF4基因的联合作用显著增加了ARC的易感性。经过多重校正以后,仅有HSF4的CNV与ARC的易感性有关,尤其与核性和后囊下性ARC的易感性有关。结论 HSF4基因与WRN基因的CNV可能与中国汉族人群ARC的易感性有关。DNA修复基因对ARC易感性有一定的作用,并且对不同亚型ARC产生不同的影响。

Copy number variations of DNA repair genes and its relationship with the age-related cataract

Objective　To examine the association of copy number variations (CNV) of DNA repair genes with susceptibility to age-related cataract (ARC) in the Han Chinese.Methods　Study participants were from the population-based Jiangsu Eye Study,which included 780 ARC patients and 525 controls.DNA was extracted from blood for copy number (CN) assays using RT-PCR.The odds ratios (OR) were calculated to estimate the genotype distributions of CNV between ARC patients and normal controls.Results　Novel CNV were detected in WRN.Initial analyses found that CN=3+ for WRN had an increased risk of ARC vulnerability (OR=1.88,P=0.02).CN=1 for HSF4 had an increased risk of ARC vulnerability (OR=4.09,P=0.004).CN=3+ for WRN was associated with nuclear and posterior subcapsular cataract (OR=2.06,3.72,both P=0.02).CN=1 for HSF4 was associated with nuclear and posterior subcapsular cataract (OR=5.73,P=0.001 and OR=6.80,P=0.01).The combination WRN and HSF4 CNV markedly increased the risk of ARC.However,after multiple testing correction,only HSF4 CNV were associated with ARC overall and with nuclear and posterior subcapsular cataract as well.Conclusion　HSF4 and WRN CNV may 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.