年龄相关性白内障人群DNA损伤修复基因与环境因素的交互作用

Study on gene-gene, gene-environmental interactions of DNA repair genes related with age-related cataract

目的探讨基因-基因、基因-环境交互作用在年龄相关性白内障（ARC）发生中的作用。方法采用人群为基础的病例-对照研究设计。收集江苏省阜宁县眼病研究数据库（现场工作于2010年6月至2011年5月进行）中448例白内障患者作为病例组，284例与患者年龄、性别相匹配且无亲属关系的为对照组。采用实时荧光PCR（RT—PCR）方法检测基因WRN、OGGl、BLM以及ERCC6等18个位点单核甘酸多态性。问卷调查收集研究对象的特征、生活行为习惯、既往病史、既往阳光照射时间等环境因素。非条件Logistic回归和多因子降维法（MDR）评价基因-基因、基因-环境交互作用。结果单环境因素作用：受教育程度与ARC的发病相关，文盲较非文盲ARC风险增加，差异有统计学意义（OR=1．53，P〈0．05）；农民发生ARC的风险是非农民的3．75倍；既往阳光照射时间与ARC的发病存在正相关关系；未发现吸烟、饮酒、高血压等因素与ARC患病相关（P〉0．05）。单基因作用：经Bonferroni多重检验校正后，除了WRN—rsll574311位点（OR=1．98，Pa〈0．018），其余位点差异均无统计学意义。基因-环境交互作用：MDR最佳交互作用模型包含既往阳光照射时间、受教育程度、WRN—rs11574311、WRN-rs1801195、WRN-rs4733220以及BLM-rsl7273206的6个因子模型（平均检验准确度为0．683，交叉验证-致性为10／10，P=0．005）。研究对象经以上6个因子组合后，在风险度上区分为“高风险”和“低风险”两个组合。高、低风险组合分别合并，Logistic分析表明，与低风险组合相比，高风险组合可以使ARC的患病风险增高（OR=5．51，P〈0．05）。结论WRN-rs11574311突变等位基因是江苏省阜宁县发生ARC的危险等位基因；同时携带WRN-rs18011951、WRN-rs4733220及日mz-rs17273206突变等位基因、教育程度低以及既往阳光照射时间长的个体罹患ARC风险显著增加。

Objective To investigate the interaction between polymorphisms and environment factors in age related cataract （ ARC ）. Methods Population-based case-control study. All of 448 cataract cases were selected from cataract eye database and 248 controls were recruited from Funing county. All 18 single nueleotide polymorphism （SNPs） of WRN, OGG1, BLM and ERCC6 genes were genotyped using real-time fluorescent quantitative PCR. The possible risk of ARC was estimated by unconditional Logistic regression. The interaction effects between gene-gene and gene-environment were evaluated by use of multifactor dimensionality reduction （ MDR）. Results Risk of ARC in illiterate group was significantly increased （ OR = 1.53, P 〈 0. 05 ） , compared to noilliterate group. The risk of cataract in farmers was significantly high with ORs of 3.75. Long exposure to sunlight may increase cataract risk. Factors such as smoking, drinking, hypertension had no relationship with ARC （P 〉 0. 05 ）. WRN-rsl1574311 was still associated with ARC with statistical significance after Bonferroni correction （ OR = 1.98 ,Pa 〈 0. 018）. There was no evidence for any association at a significance level of P 〈 0.05 for the remaining alleles. MDR analysis showed a significant interaction model among the six factors： education, solar radiation, WRN- rs11574311, WRN-rs1801195, WRN-rs4733220 and BLM-rs17273206 （consistency inspection accuracy of 0. 683 on average, cross validation at 10/10, P = 0. 005 ）. Logistic regression model showed that the ＂high- risk＂ individuals had a significantly increased risk of ARC, compared to those ＂low- risk＂ individual classified by the MDR mode mentioned above（OR =5.51 ,P〈0.05）. Conclusion WRN-rsl1574311 allele was the risk factor for ARC, and individuals who carried WRN-rs1801195, WRN-rs4733220 and BLM- rs17273206 allele and low level of education, long sunlight time significantly increased the risk of the ARC.