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Luis E. Vazquez, Corina J. Shtir, Cathy Wu, Mina Torres, Roberta McKean-Cowdin, Rohit Varma; The Y402H Polymorphism in Complement Factor H and Primary Open Angle Glaucoma: The Los Angeles Latino Eye Study (LALES). Invest. Ophthalmol. Vis. Sci. 2011;52(14):1644.
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Recent data suggests that the complement cascade plays a role in pathogenesis of glaucoma. Retinal ganglion cells (RGCs) express C1q in response to high intraocular pressure (IOP), which targets dendritic RGC terminals for destruction early in disease. We therefore hypothesize that individuals with deficits in complement inhibition are at risk of developing glaucoma. Here, we show that the Y402H single nucleotide polymorphism (SNP) in complement factor H (CFH), previously associated with age-related macular Degeneration (AMD), may also be associated with primary open angle glaucoma (POAG).
156 AMD cases and 270 controls were selected from the LALES cohort. AMD cases were identified based on age related eye disease study scale (AREDS) scores>7; controls had AREDS score=0. POAG cases were identified based on evidence of glaucomatous damage in disc photos and visual fields, evaluated by an external glaucoma committee. The Y402H genotype (TT, CT or CC) was obtained from an Illumina Array of 389 SNPs. Based on the literature, we considered the C allele as risk for both AMD and POAG. We examined the frequency of C allele genotypes (risk genotypes) by disease status: AMD cases, POAG cases, AMD+POAG cases, and controls without AMD or POAG. Chi-square tests were used to determine significant differences in risk genotype frequencies by disease status. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals adjusting for matching factors. Analysis was performed using a 5% significance level.
The frequency of risk genotypes in controls, POAG, AMD, and POAG+AMD cases were 0.33, 0.36, 0.41 and 0.69, respectively. We found a statistically significant difference in the frequency of risk genotypes for cases with both AMD and POAG compared to controls (Chi square, p=0.01). We also found an elevated OR for risk genotypes for individuals with both AMD and POAG (OR=1.5; p<0.05); AMD alone (OR=1.3; p=0.20). The association between risk genotypes and POAG (regardless of AMD status) was similarly elevated (OR 1.9, p=0.07). While this finding is based on small numbers of POAG, it suggests that the Y402H SNP may be also associated with POAG. Our sample size of POAG and POAG+AMD was small (N=22 and N=13 respectively) and need further investigation in a larger sample.
We show that Y402H may be associated with POAG, suggesting that individuals with deficiencies in complement inhibition are at risk of glaucoma.
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