title: Role of an extracellular chaperone, Clusterin in the pathogenesis of Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma.
abstract: 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.
authors: School of Biological Sciences, NISER, Bhubaneswar, Odisha, India.
authors: Biswajit
authors: B
authors: Padhy
authors: School of Biological Sciences, NISER, Bhubaneswar, Odisha, India.
authors: Gargi G
authors: GG
authors: Nanda
authors: Glaucoma Services, LV Prasad Eye Institute, Bhubaneswar, Odisha, India.
authors: Mahasweta
authors: M
authors: Chowdhury
authors: Glaucoma Services, LV Prasad Eye Institute, Bhubaneswar, Odisha, India.
authors: Debanand
authors: D
authors: Padhi
authors: Glaucoma Services, LV Prasad Eye Institute, Bhubaneswar, Odisha, India. Electronic address: aparna@lvpei.org.
authors: Aparna
authors: A
authors: Rao
authors: School of Biological Sciences, NISER, Bhubaneswar, Odisha, India. Electronic address: debasmita@niser.ac.in.
authors: Debasmita P
authors: DP
authors: Alone
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001082:Aqueous Humor / Q000378:metabolism; D016022:Case-Control Studies; D051152:Clusterin / Q000235:genetics* / Q000378:metabolism; D017889:Exfoliation Syndrome / Q000235:genetics*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005786:Gene Expression Regulation / Q000502:physiology*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006801:Humans; D007429:Intraocular Pressure; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D014065:Tonometry, Ocular; D014794:Visual Fields
chemical_list: C495242:CLU protein, human; D051152:Clusterin; D012333:RNA, Messenger
keywords: Indian population; clusterin; glaucoma; pseudoexfoliation