Padhy Biswajit, Nanda Gargi G, Chowdhury Mahasweta, Padhi Debanand, Rao Aparna, Alone Debasmita P
School of Biological Sciences, NISER, Bhubaneswar, Odisha, India.
Glaucoma Services, LV Prasad Eye Institute, Bhubaneswar, Odisha, India.
Exp Eye Res. 2014 Oct;127:69-76. doi: 10.1016/j.exer.2014.07.005. Epub 2014 Jul 21.
Pseudoexfoliation (PEX), an age related disorder is a prominent contributor to secondary glaucoma. Earlier studies have suggested involvement of clusterin in the development of PEX. We designed a case-control study to understand the role of clusterin single nucleotide polymorphisms (SNPs) in PEX and analyzed the role of risk alleles in the disease. Genotyping of SNPs in 136 PEX patients and 89 controls of Indian origin revealed a genetic association between rs2279590 and PEX in Indian population with a p-value of 0.004. The high risk allele "G" at rs2279590 has an effect on clusterin mRNA expression. There was a twofold higher clusterin mRNA level in "GG" genotyped individuals in comparison to "AA" genotyped individuals (p = 0.039). Western blot and immunohistochemistry studies showed an upregulation of Clusterin protein in pseudoexfoliation glaucoma (PXG) affected individuals in both aqueous humor and lens capsules respectively. Together, our results reveal that rs2279590 was found to be associated with PEX in Indian population and the risk allele mediates an allele specific upregulation of the clusterin mRNA. Moreover, upregulation of Clusterin protein in PXG individuals augments further protein deposition.
假性剥脱（PEX）是一种与年龄相关的疾病，是继发性青光眼的主要促成因素。早期研究表明簇集素参与了PEX的发展。我们设计了一项病例对照研究，以了解簇集素单核苷酸多态性（SNP）在PEX中的作用，并分析了风险等位基因在该疾病中的作用。对136名印度裔PEX患者和89名对照者的SNP进行基因分型，结果显示rs2279590与印度人群中的PEX存在遗传关联，p值为0.004。rs2279590处的高风险等位基因“G”对簇集素mRNA表达有影响。与“AA”基因型个体相比，“GG”基因型个体的簇集素mRNA水平高出两倍（p = 0.039）。蛋白质印迹和免疫组织化学研究表明，在假性剥脱性青光眼（PXG）患者的房水和晶状体囊中，簇集素蛋白分别上调。总之，我们的结果表明，rs2279590与印度人群中的PEX相关，风险等位基因介导了簇集素mRNA的等位基因特异性上调。此外，PXG个体中簇集素蛋白的上调进一步增加了蛋白质沉积。
