Wu Xiaohang, Lai Weiyi, Lin Haotian, Liu Yizhi
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
PLoS One. 2017 Mar 2;12(3):e0172092. doi: 10.1371/journal.pone.0172092. eCollection 2017.
To discern and confirm genetic biomarkers that help identify populations at high risk for age-related cataract (ARC).
A literature search was performed in the PubMed, Web of Science and China National Knowledge Internet databases for genetic association studies published before June 26, 2016 regarding ARC susceptibility. All genetic polymorphisms reported were systematically reviewed, followed by extraction of candidate genes/loci with sufficient genotype data in ≥3 studies for the meta-analysis. A random/fixed-effects model was used to calculate the pooled odds ratios and 95% confidence intervals to evaluate the associations considering multiple genetic models. Sensitivity analysis was also performed.
A total of 144 polymorphisms in 36 genes were reported in the 61 previous genetic association studies. Thereby, three polymorphisms of two genes (8-oxoguanine DNA glycosylase-1 [OGG1]; methylenetetrahydrofolate reductase NADPH [MTHFR]) in eight studies were included in the meta-analysis. Regarding the OGG1-rs1052133, the GG (OR = 1.925; 95%CI, 1.181-3.136; p = 0.009) and CG (OR = 1.384; 95%CI, 1.171-1.636; p<0.001) genotypes indicated higher risk of ARC. For the MTHFR gene, the CC+TT genotype of rs1801133 might be protective (OR, 0.838; 95%CI, 0.710-0.989; p = 0.036), whereas the AA+CC genotype of rs1801131 indicated increased risk for the mixed subtype (OR = 1.517; 95%CI, 1.113-2.067; p = 0.008).
Polymorphisms of OGG1 and MTHFR genes are associated with ARC susceptibility and may help identify populations at high risk for ARC.
识别并确认有助于确定年龄相关性白内障(ARC)高危人群的遗传生物标志物。
在PubMed、科学网和中国知网数据库中检索2016年6月26日前发表的关于ARC易感性的遗传关联研究。对所有报道的基因多态性进行系统综述,随后提取在≥3项研究中有足够基因型数据的候选基因/位点进行荟萃分析。采用随机/固定效应模型计算合并比值比和95%置信区间,以评估考虑多种遗传模型时的关联性。还进行了敏感性分析。
之前的61项遗传关联研究共报道了36个基因中的144个多态性。因此,八项研究中两个基因(8-氧代鸟嘌呤DNA糖基化酶-1 [OGG1];亚甲基四氢叶酸还原酶NADPH [MTHFR])的三个多态性被纳入荟萃分析。关于OGG1-rs1052133,GG(OR = 1.925;95%CI,1.181 - 3.136;p = 0.009)和CG(OR = 1.384;95%CI,1.171 - 1.636;p<0.001)基因型表明ARC风险较高。对于MTHFR基因,rs1801133的CC + TT基因型可能具有保护作用(OR,0.838;95%CI,0.710 - 0.989;p = 0.036),而rs1801131的AA + CC基因型表明混合亚型风险增加(OR = 1.517;95%CI,1.113 - 2.067;p = 0.008)。
OGG1和MTHFR基因的多态性与ARC易感性相关,可能有助于识别ARC高危人群。