title: Association of known common genetic variants with primary open angle, primary angle closure, and pseudoexfoliation glaucoma in Pakistani cohorts.
abstract: OBJECTIVE
  Despite the different etiology of primary open angle glaucoma (POAG), primary angle closure glaucoma (PACG), and pseudoexfoliative glaucoma (PEXG), several studies have suggested that these forms of glaucoma have overlapping genetic risk factors. Therefore, the aim of this study was to evaluate the role of genetic variants recently associated with POAG in different types of glaucoma in Pakistani POAG, PACG, and PEXG patient cohorts.
  
  
  METHODS
  Six variants in CDKN2B-AS1 (rs4977756), CDKN2B (rs1063192), ATOH7 (rs1900004), CAV1 (rs4236601), TMCO1 (rs4656461), and SIX1 (rs10483727) were genotyped using TaqMan assays. A total of 513 unrelated patients with glaucoma (268 with POAG, 125 with PACG, and 120 with PEXG) and 233 healthy controls were included in the study. Genotypic and allelic associations were analyzed with a chi-square test.
  
  
  RESULTS
  The frequency of the G allele of TMCO1 rs4656461 was significantly lower in the patients with POAG (p=0.003; OR [odds ratio]=0.57), PACG (p=0.009; OR=0.52), and PEXG (p=0.01; OR=0.54) compared to the control individuals. The T allele of ATOH7 rs1900004 was observed less frequently in the patients with PACG (p=0.03; OR=0.69) compared to the control individuals. The A allele of CAV1 rs4236601 was found more frequently in the patients with POAG (p=0.008; OR=1.49) compared to the control individuals. This study demonstrates that the TMCO1 rs4656461 variant is associated with POAG, PACG and PEXG in the Pakistani population. Our study was unable to confirm previous associations reported for variants in CDKN2B-AS1, CDKN2B, and SIX1 with any type of glaucoma.
  
  
  CONCLUSIONS
  In conclusion, we found consistent evidence of the significant association of three common variants in TMCO1, ATOH7, and CAV1.
authors.affiliation: Department of Ophthalmology, Radboud University Medical Centre, Nijmegen, the Netherlands.
authors.forename: Shazia
authors.initials: S
authors.lastname: Micheal
authors.affiliation: Department of Ophthalmology, Radboud University 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: Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan ; Department of Human Genetics, Radboud University Medical Centre, Nijmegen, the Netherlands.
authors.forename: Muhammad Imran
authors.initials: MI
authors.lastname: Khan
authors.affiliation: Department of Ophthalmology, Radboud University Medical Centre, Nijmegen, the Netherlands.
authors.forename: Bjorn
authors.initials: B
authors.lastname: Bakker
authors.affiliation: Department of Ophthalmology, Radboud University Medical Centre, Nijmegen, the Netherlands.
authors.forename: Frederieke E
authors.initials: FE
authors.lastname: Schoenmaker-Koller
authors.affiliation: Al-Shifa Trust Eye Hospital Jhelum Road, Rawalpindi, Pakistan.
authors.forename: Mahmood
authors.initials: M
authors.lastname: Ali
authors.affiliation: Al-Shifa Trust Eye Hospital Jhelum Road, Rawalpindi, Pakistan.
authors.forename: Farah
authors.initials: F
authors.lastname: Akhtar
authors.affiliation: Al-Shifa Trust Eye Hospital Jhelum Road, Rawalpindi, Pakistan.
authors.forename: Wajid Ali
authors.initials: WA
authors.lastname: Khan
authors.affiliation: Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.
authors.forename: Raheel
authors.initials: R
authors.lastname: Qamar
authors.affiliation: Department of Ophthalmology, Radboud University Medical Centre, Nijmegen, the Netherlands ; Department of Human Genetics, Radboud University Medical Centre, Nijmegen, the Netherlands.
authors.forename: Anneke I
authors.initials: AI
authors.lastname: den Hollander
mesh_terms: D000483:Alleles; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D015220:Calcium Channels; D016022:Case-Control Studies; D051242:Caveolin 1 / Q000235:genetics*; D015331:Cohort Studies; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics; D017889:Exfoliation Syndrome / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D015812:Glaucoma, Angle-Closure / Q000235:genetics* / Q000473:pathology; D005902:Glaucoma, Open-Angle / Q000235:genetics* / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D010154:Pakistan; D020641:Polymorphism, Single Nucleotide
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015220:Calcium Channels; D051242:Caveolin 1; D050762:Cyclin-Dependent Kinase Inhibitor p15; D018398:Homeodomain Proteins; D008565:Membrane Proteins; C456975:ATOH7 protein, human; C495540:CAV1 protein, human; C493966:CDKN2B protein, human; C099236:SIX1 protein, human; C575495:TMCO1 protein, human