title: Association of a polymorphism in the BIRC6 gene with pseudoexfoliative glaucoma.
abstract: Recently an association was observed between alleles in genes of the unfolded protein response pathway and primary open angle glaucoma (POAG). The goal of the current study is to investigate the role of these two genes, protein disulphide isomerase A member 5 (PDIA5) and baculoviral IAP repeat containing 6 (BIRC6), in different forms of glaucoma. 278 patients with POAG, 132 patients with primary angle closure glaucoma (PACG) and 135 patients with pseudoexfoliative glaucoma (PEXG) were genotyped for single nucleotide polymorphisms (SNPs) rs11720822 in PDIA5 and 471 POAG, 184 PACG and 218 PEXG patients were genotyped for rs2754511 in BIRC6. Genotyping was done by allelic discrimination PCR, and genotype and allele frequencies were calculated. Logistic regression analyses were performed using R software to determine the association of these SNPs with glaucoma. The allele and genotype frequencies of rs11720822 in PDIA5 were not associated with POAG, PACG or PEXG. The TT genotype of rs2754511 in BIRC6 was found to be protective for PEXG (p = 0.05, OR 0.42 [0.22-0.81]) in the Pakistani population, but not for POAG or PACG. This study did not confirm a previously reported association of risk alleles in PDIA5 and BIRC6 with POAG, but did demonstrate a protective role of the T allele of rs2754511 in the BIRC6 gene in PEXG. This supports a role for the unfolded protein response pathway and regulation of apoptotic cell death in the pathogenesis of PEXG.
authors.affiliation: Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.
authors.forename: Humaira
authors.initials: H
authors.lastname: Ayub
authors.affiliation: Department of Ophthalmology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Shazia
authors.initials: S
authors.lastname: Micheal
authors.affiliation: Al-Shifa Trust Eye Hospital, Rawalpindi, Pakistan.
authors.forename: Farah
authors.initials: F
authors.lastname: Akhtar
authors.affiliation: Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Muhammad Imran
authors.initials: MI
authors.lastname: Khan
authors.affiliation: Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.
authors.forename: Shaheena
authors.initials: S
authors.lastname: Bashir
authors.affiliation: Department of Ophthalmology, Tufts University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Nadia K
authors.initials: NK
authors.lastname: Waheed
authors.affiliation: Al-Shifa Trust Eye Hospital, Rawalpindi, Pakistan.
authors.forename: Mahmood
authors.initials: M
authors.lastname: Ali
authors.affiliation: Department of Ophthalmology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Frederieke E
authors.initials: FE
authors.lastname: Schoenmaker-Koller
authors.affiliation: Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.
authors.forename: Sobia
authors.initials: S
authors.lastname: Shafique
authors.affiliation: Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan; Al-Nafees Medical College & Hospital, Isra University, Islamabad, Pakistan.
authors.forename: Raheel
authors.initials: R
authors.lastname: Qamar
authors.affiliation: Department of Ophthalmology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Anneke I den
authors.initials: AI
authors.lastname: Hollander
mesh_terms: D000328:Adult; D017889:Exfoliation Syndrome / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005901:Glaucoma / Q000235:genetics*; D015812:Glaucoma, Angle-Closure / Q000235:genetics; D005902:Glaucoma, Open-Angle / Q000235:genetics; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D019704:Protein Disulfide-Isomerases / Q000235:genetics
chemical_list: C401541:BIRC6 protein, human; D051034:Inhibitor of Apoptosis Proteins; C526506:PDIA5 protein, human; D019704:Protein Disulfide-Isomerases