title: Variants in the ASB10 Gene Are Associated with Primary Open Angle Glaucoma.
abstract: BACKGROUND
  Recently nonsynonymous coding variants in the ankyrin repeats and suppressor of cytokine signaling box-containing protein 10 (ASB10) gene were found to be associated with primary open angle glaucoma (POAG) in cohorts from Oregon and Germany, but this finding was not confirmed in an independent cohort from Iowa. The aim of the current study was to assess the role of ASB10 gene variants in Pakistani glaucoma patients.
  
  
  METHODS
  Sanger sequencing of the coding exons and splice junctions of the ASB10 gene was performed in 30 probands of multiplex POAG families, 208 sporadic POAG patients and 151 healthy controls from Pakistan. Genotypic associations of individual variants with POAG were analyzed with the Fisher's exact or Chi-square test.
  
  
  RESULTS
  In total 24 variants were identified in POAG probands and sporadic patients, including 11 novel variants and 13 known variants. 13 of the variants were nonsynonymous, 6 were synonymous, and 5 were intronic. Three nonsynonymous variants (p.Arg49Cys, p.Arg237Gly, p.Arg453Cys) identified in the probands were not segregating in the respective families. This is not surprising since glaucoma is a multifactorial disease, and multiple factors are likely to be involved in the disease manifestation in these families. However a nonsynonymous variant, p.Arg453Cys (rs3800791), was found in 6 sporadic POAG patients but not in controls, suggesting that it infers increased risk for the disease. In addition, one synonymous variant was found to be associated with sporadic POAG: p.Ala290Ala and the association of the variant with POAG remained significant after correction for multiple testing (uncorrected p-value 0.002, corrected p-value 0.047). The cumulative burden of rare, nonsynonymous variants was significantly higher in sporadic POAG patients compared to control individuals (p-value 0.000006).
  
  
  CONCLUSIONS
  Variants in ASB10 were found to be significantly associated with sporadic POAG in the Pakistani population. This supports previous findings that sequence variants in the ASB10 gene may act as a risk factor for glaucoma.
authors.affiliation: Department of Ophthalmology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
authors.forename: Shazia
authors.initials: S
authors.lastname: Micheal
authors.affiliation: Department of Ophthalmology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.|Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.
authors.forename: Humaira
authors.initials: H
authors.lastname: Ayub
authors.affiliation: Al-Shifa Eye Trust Hospital Jhelum Road, Rawalpindi, 46000, Pakistan.
authors.forename: Farrah
authors.initials: F
authors.lastname: Islam
authors.affiliation: Al-Shifa Eye Trust Hospital Jhelum Road, Rawalpindi, 46000, Pakistan.
authors.forename: Sorath Noorani
authors.initials: SN
authors.lastname: Siddiqui
authors.affiliation: Al-Shifa Eye Trust Hospital Jhelum Road, Rawalpindi, 46000, Pakistan.
authors.forename: Wajid Ali
authors.initials: WA
authors.lastname: Khan
authors.affiliation: Al-Shifa Eye Trust Hospital Jhelum Road, Rawalpindi, 46000, Pakistan.
authors.forename: Farah
authors.initials: F
authors.lastname: Akhtar
authors.affiliation: Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.|Al-Nafees Medical College & Hospital, Isra University, Islamabad, 45600, Pakistan.
authors.forename: Raheel
authors.initials: R
authors.lastname: Qamar
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 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
authors.initials: AI
authors.lastname: den Hollander
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D015331:Cohort Studies; D005260:Female; D014644:Genetic Variation; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D050826:Suppressor of Cytokine Signaling Proteins / Q000737:chemistry / Q000235:genetics*; D055815:Young Adult
chemical_list: C574092:ASB10 protein, human; D050826:Suppressor of Cytokine Signaling Proteins