Zhou Zhou, Wang Binbin, Hu Shanshan, Zhang Chunmei, Ma Xu, Qi Yanhua
Department of Ophthalmology, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Mol Vis. 2011 Feb 26;17:621-6.
To investigate the role of genetic variations in three known cataract-associated genes, gap junction protein α3 (GJA3), gap junction protein α8 (GJA8), lens intrinsic membrane protein 2 (LIM2), encoding lens fiber cell membrane proteins in the development of age-related cataracts.
One hundred and forty-five sporadic age-related cataract patients and one hundred and fifty-six unrelated random healthy controls participated in this study. Genomic DNA was extracted from peripheral blood leukocytes. All exons of GJA3, GJA8, and LIM2 were sequenced after being amplified by polymerase chain reaction (PCR). The functional consequences of the mutations were analyzed using PolyPhen.
We found five novel variations in 145 patients and none of them presented in the 156 controls. There are two variations in GJA3 (c.-39C>G, c. 415G>A); one in GJA8 (c. 823G>A), and two in LIM2 (c.57G>A, c.67A>C). PolyPhen predicted that the LIM2 c.67A>C mutation may have potential pathogenicity.
The genetic mutation in GJA3, GJA8, and LIM2 may slightly contribute to the development of age-related cataracts. This study showed a potential relationship between lens fiber cell membrane protein genes and the development of age-related cataracts in the Chinese population.
研究三个已知的白内障相关基因，即缝隙连接蛋白α3（GJA3）、缝隙连接蛋白α8（GJA8）、晶状体固有膜蛋白2（LIM2）（编码晶状体纤维细胞膜蛋白）的基因变异在年龄相关性白内障发生发展中的作用。
145例散发性年龄相关性白内障患者和156例无亲缘关系的随机健康对照参与了本研究。从外周血白细胞中提取基因组DNA。通过聚合酶链反应（PCR）扩增后，对GJA3、GJA8和LIM2的所有外显子进行测序。使用PolyPhen分析突变的功能后果。
我们在145例患者中发现了5个新的变异，而在156例对照中均未出现。GJA3中有两个变异（c.-39C>G，c.415G>A）；GJA8中有一个变异（c.823G>A），LIM2中有两个变异（c.57G>A，c.67A>C）。PolyPhen预测LIM2基因的c.67A>C突变可能具有潜在致病性。
GJA3、GJA8和LIM2基因的突变可能对年龄相关性白内障的发生发展有轻微影响。本研究显示了晶状体纤维细胞膜蛋白基因与中国人群年龄相关性白内障发生发展之间的潜在关系。
