title: A Genetic Variant in TGFBR3-CDC7 Is Associated with Visual Field Progression in Primary Open-Angle Glaucoma Patients from Singapore.
abstract: OBJECTIVE
  To investigate whether known genetic loci for primary open-angle glaucoma (POAG) are associated with visual field (VF) progression in patients from a Singaporean Chinese population.
  
  
  METHODS
  Retrospective study.
  
  
  METHODS
  Patients with 5 or more reliable VF measurements who were being followed up at a Singapore hospital.
  
  
  METHODS
  Visual field progression was identified using Progressor software version 3.7 (Medisoft, Leeds, United Kingdom) and defined by pointwise linear regression (PLR) criteria as follows: any 2 contiguous points in the same hemifield progressing (≤-1.00 dB/year for inner points and ≤-2.00 dB/year for edge points; P < 0.01). Single nucleotide polymorphisms (SNPs) and their proxies from 10 POAG-associated loci (CAV1-CAV2, CDKN2B-AS1, SIX1-SIX6, an intergenic region on chromosome 8q22, ABCA1, GAS7, AFAP1, GMDS, PMM2, and TGFBR3-CDC7) identified from genome-wide association studies were tested for association with VF progression using logistic regression with an additive genetic model adjusting for age, gender, average intraocular pressure (IOP), central corneal thickness (CCT), and baseline vertical cup-to-disc ratio (VCDR).
  
  
  METHODS
  Visual field progression.
  
  
  RESULTS
  Of the 1334 patients included in the study, 469 subjects (35.1%) completed 5 or more reliable VF measurements (mean follow-up, 9.01 years; standard deviation, 5.00 years). The mean age of patients was 59.6 years (standard deviation, 9.0 years); 305 patients were men and all were Chinese. The average IOP in eyes fulfilling PLR progression was 16.5 mmHg versus 17.7 mmHg in those who did not (P = 0.52). Univariate analysis revealed that increased VCDR (P = 0.003), reduced CCT (P = 0.045), and reduced superior and inferior retinal nerve fiber layer thickness (P = 0.01, respectively) were associated with VF progression. No clinical or structural features were associated significantly with VF progression on multivariate analysis. The rs1192415 index SNP in TGFBR3-CDC7 (P = 0.002; odds ratio, 6.71 per risk allele) was the only SNP associated with VF progression.
  
  
  CONCLUSIONS
  The presence of the index SNP rs1192415 (TGFBR3-CDC7) was associated with VF progression in POAG patients. These findings warrant further investigation in independent cohorts.
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Republic of Singapore.
authors.forename: Sameer
authors.initials: S
authors.lastname: Trikha
authors.affiliation: Duke-NUS Graduate Medical School, Singapore, Republic of Singapore.
authors.forename: Ehsan
authors.initials: E
authors.lastname: Saffari
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Republic of Singapore.
authors.forename: Monisha
authors.initials: M
authors.lastname: Nongpiur
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Republic of Singapore.
authors.forename: Mani
authors.initials: M
authors.lastname: Baskaran
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Republic of Singapore.
authors.forename: Henrietta
authors.initials: H
authors.lastname: Ho
authors.affiliation: Genome Institute Singapore, Singapore, Republic of Singapore.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Republic of Singapore.
authors.forename: Peng-Yi
authors.initials: PY
authors.lastname: Tan
authors.affiliation: Duke-NUS Graduate Medical School, Singapore, Republic of Singapore.
authors.forename: John
authors.initials: J
authors.lastname: Allen
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Republic of Singapore; Genome Institute Singapore, Singapore, Republic of Singapore.
authors.forename: Chiea-Chuen
authors.initials: CC
authors.lastname: Khor
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Republic of Singapore.
authors.forename: Shamira A
authors.initials: SA
authors.lastname: Perera
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Republic of Singapore; Duke-NUS Graduate Medical School, Singapore, Republic of Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore.
authors.forename: Ching-Yu
authors.initials: CY
authors.lastname: Cheng
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Republic of Singapore; Duke-NUS Graduate Medical School, Singapore, Republic of Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore. Electronic address: aung.tin@snec.com.sg.
authors.forename: Tin
authors.initials: T
authors.lastname: Aung
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Republic of Singapore; Duke-NUS Graduate Medical School, Singapore, Republic of Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore.
authors.forename: Eranga
authors.initials: E
authors.lastname: Vithana
mesh_terms: D000368:Aged; D018797:Cell Cycle Proteins / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D003315:Cornea / Q000473:pathology; D063171:Corneal Pachymetry; D021901:DNA, Intergenic / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers / Q000235:genetics; D060005:Genotyping Techniques; D005902:Glaucoma, Open-Angle / Q000175:diagnosis / Q000235:genetics*; D006068:Gonioscopy; D006801:Humans; D007429:Intraocular Pressure; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011509:Proteoglycans / Q000235:genetics*; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D012189:Retrospective Studies; D012846:Singapore; D014065:Tonometry, Ocular; D014786:Vision Disorders / Q000175:diagnosis*; D058609:Visual Field Tests; D014794:Visual Fields
chemical_list: D018797:Cell Cycle Proteins; D021901:DNA, Intergenic; D005819:Genetic Markers; D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; C071736:betaglycan; C068619:CDC7 protein, human; D017346:Protein Serine-Threonine Kinases