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Sameer Trikha, Ehsan Saffari, Henrietta Ho, Monisha Esther Nongpiur, Baskaran Mani, John Allen, Ching-Yu Cheng, Tin Aung, Eranga Nishanthie Vithana; . Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4382. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To identify genetic determinants of visual field (VF) progression in primary open angle glaucoma (POAG) patients of Chinese ancestry.
Visual fields of 1335 POAG patients, genotyped on Illumina Omniexpress arrays (Illumina,Ca,USA), were analysed for progression using Progressor software (Progressor,Leeds,UK). Only patients with 5 or more reliable Standard Automated Perimetry VFs (SITA 24-2) were included for analysis. The overall rate of mean deviation(MD) change (dB/year) was evaluated, and the pointwise linear regression criteria of any two contiguous points progressing within the same hemifield was used to define progression. Points were deemed progressing if there was a loss of ≥ -0.1dB/yr for non-edge points and ≥-0.2dB/year for edge points (p<0.05). Lead SNPs (single nucleotide polymorphism) and their proxies from all 10 POAG associated loci (CAV1-CAV2, TMCO1, CDKN2B-AS1, SIX1-SIX6, an intergenic region on chromosome 8q22, ABCA1, GAS7, AFAP1, GMDS,PMM2) known to date from genome-wide association studies, in addition to the recently identified but not yet reported TGFBR3-CDC7 locus from our group, 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 and baseline vertical cup disc ratio (VCDR).
469 study eyes completed 5 or more reliable VFs (mean 9.01 yrs, SD 5.00 yrs). The overall MD rate of progression of the cohort was -0.13dB/yr. 68 eyes (14.5%) fulfilled the criteria for POAG progression. The average IOP in eyes fulfilling the progression criteria was 15.68 mmHg vs. 16.54 mmHg in those who did not (p=0.228). A total of 25 SNPs were significantly associated with VF progression. This included rs1192404 in TGFBR3 (p=0.0018; odds ratio (OR) 4.24 per risk allele), that has been strongly associated with VCDR, and rs1041159 (p=0.0081; OR 3.18/allele) which it is in linkage disequilibrium (LD) with (r2 0.96). SNP rs3800101 (p=0.0048; OR 2.59/allele), in GMDS on chromosome 6, was also associated with fulfilling the criteria for VF progression.
The presence of SNPs rs1192404, in LD with rs1041159 (TGFBR3-CDC7), and rs3800101(GMDS) were associated with greater VF progression in this Chinese POAG cohort. These findings warrant further investigation in independent cohorts.
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