Sameer Trikha1, Ehsan Saffari2, Monisha Nongpiur1, Mani Baskaran1, Henrietta Ho1, Zheng Li3, Peng-Yi Tan1, John Allen2, Chiea-Chuen Khor4, Shamira A Perera1, Ching-Yu Cheng5, Tin Aung6, Eranga Vithana5. 1. Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Republic of Singapore. 2. Duke-NUS Graduate Medical School, Singapore, Republic of Singapore. 3. Genome Institute Singapore, Singapore, Republic of Singapore. 4. Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Republic of Singapore; Genome Institute Singapore, Singapore, Republic of Singapore. 5. 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. 6. 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.
Abstract
PURPOSE: 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. DESIGN: Retrospective study. PARTICIPANTS: 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). MAIN OUTCOME MEASURE: 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.
PURPOSE: 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. DESIGN: Retrospective study. PARTICIPANTS: 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). MAIN OUTCOME MEASURE: 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: Jamila Alessandra Perini; Mayara Calixto Silva; Ana Claudia Santiago de Vasconcellos; Paulo Victor Sousa Viana; Marcelo Oliveira Lima; Iracina Maura Jesus; Joseph William Kempton; Rogério Adas Ayres Oliveira; Sandra Souza Hacon; Paulo Cesar Basta Journal: Int J Environ Res Public Health Date: 2021-08-19 Impact factor: 3.390
Authors: Valeria Lo Faro; Ilja M Nolte; Jacoline B Ten Brink; Harold Snieder; Nomdo M Jansonius; Arthur A Bergen Journal: Front Genet Date: 2021-12-16 Impact factor: 4.599