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Abstract #58820 Published in IGR 16-3

Role of an extracellular chaperone, Clusterin in the pathogenesis of Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma

Padhy B; Nanda GG; Chowdhury M; Padhi D; Rao A; Alone DP
Experimental Eye Research 2014; 127: 69-76

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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.

School of Biological Sciences, NISER, Bhubaneswar, Odisha, India.

Full article

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Classification:

9.4.4.1 Exfoliation syndrome (Part of: 9 Clinical forms of glaucomas > 9.4 Glaucomas associated with other ocular and systemic disorders > 9.4.4 Glaucomas associated with disorders of the lens)
3.4.2 Gene studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)

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