Lin Qinghong, Zhou Nan, Zhang Na, Zhu Bidan, Hu Shanshan, Zhou Zhou, Qi Yanhua
Department of Ophthalmology, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Mol Vis. 2013 Jul 20;19:1572-9. Print 2013.
Age-related cataract (ARC) is a complex multifactorial disorder, including genetic and environmental factors. Ezrin (EZR), a member of the ezrin/radixin/moesin (ERM) protein family, plays a crucial role in the development of the lens as a plasma membrane-cytoskeleton linker. We conducted this study to investigate the role of genetic variations of ezrin and the relationship between single nucleotide polymorphisms (SNPs) in EZR and susceptibility to ARC in a Chinese population.
A total of 205 sporadic age-related cataract patients and 218 unrelated random healthy controls participated in our study. Genomic DNA was extracted from peripheral blood leukocytes. All exons of EZR were sequenced after being amplified with polymerase chain reaction. The functional consequences of the mutations were analyzed using PolyPhen2. SNP statistical analysis was performed using SNPstats.
We found three novel variations in 205 patients. None presented in the 218 controls, including c.441C>G, c.924G>C, and c.1503G>A. PolyPhen2 predicted that the c.924G>C mutation probably had pathogenicity. Compared with the healthy controls, the rs5881286 -/GT genotype and - allele frequencies (p=0.0012; odds ratio [OR]=3.37; 95% confidence interval [CI]=1.70-6.70; p=3.96e-5; χ(2)=18.98, respectively), rs2242318 T/C genotype and C allele frequencies (p=0.0045; OR=3.40; 95% CI=1.70-6.79; p=8.82e-6; χ(2)=21.86, respectively), and rs144581330 A/G genotype and G allele frequencies (p=0.0472; OR=14.46; 95% CI=1.29-162.43; p=0.0244, χ(2)=6.99, respectively) were higher in the patients with age-related cataract. SNP rs144581330 in exon 2 was also predicted to be probably damaging by PolyPhen2. Haplotype association including the - allele of rs5881286, C allele of rs2242318, and A allele of rs144581330 exhibited significantly higher distribution in the patients with ARC (p=8.0e-4; OR=3.38; 95% CI=1.66-6.87).
This study suggests that the genetic variations and SNPs in the gene EZR possibly contribute to the development of age-related cataracts in the Chinese population.
年龄相关性白内障（ARC）是一种复杂的多因素疾病，包括遗传和环境因素。埃兹蛋白（EZR）是埃兹蛋白/根蛋白/膜突蛋白（ERM）家族的成员，作为质膜-细胞骨架连接蛋白，在晶状体发育中起关键作用。我们开展本研究以调查埃兹蛋白基因变异的作用以及EZR基因单核苷酸多态性（SNP）与中国人群ARC易感性之间的关系。
共有205例散发性年龄相关性白内障患者和218名无血缘关系的随机健康对照参与本研究。从外周血白细胞中提取基因组DNA。用聚合酶链反应扩增后对EZR的所有外显子进行测序。使用PolyPhen2分析突变的功能后果。使用SNPstats进行SNP统计分析。
我们在205例患者中发现了3个新变异。在218名对照中均未出现，包括c.441C>G、c.924G>C和c.1503G>A。PolyPhen2预测c.924G>C突变可能具有致病性。与健康对照相比，rs5881286 -/GT基因型和 - 等位基因频率（分别为p = 0.0012；比值比[OR]=3.37；95%置信区间[CI]=1.70 - 6.70；p = 3.96e - 5；χ(2)=18.98）、rs2242318 T/C基因型和C等位基因频率（分别为p = 0.0045；OR = 3.40；95% CI = 1.70 - 6.79；p = 8.82e - 6；χ(2)=21.86）以及rs144581330 A/G基因型和G等位基因频率（分别为p = 0.0472；OR = 14.46；95% CI = 1.29 - 162.43；p = 0.0244，χ(2)=6.99）在年龄相关性白内障患者中更高。外显子2中的SNP rs144581330也被PolyPhen2预测可能具有损害性。包括rs5881286的 - 等位基因、rs2242318的C等位基因和rs144581330的A等位基因的单倍型关联在ARC患者中表现出明显更高的分布（p = 8.0e - 4；OR = 3.38；95% CI = 1.66 - 6.87）。
本研究表明，EZR基因的遗传变异和SNP可能在中国人群年龄相关性白内障的发生中起作用。
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