Purchase this article with an account.
Luis E. Vazquez, Mina Torres, Cathy Wu, Roberta McKean-Cowdin, Rohit Varma; Risk Polymorphism in SERPING1 and Primary Open Angle Glaucoma: The Los Angeles Latino Eye Study (LALES). Invest. Ophthalmol. Vis. Sci. 2012;53(14):3866.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Recent studies suggest that IOP-driven RGC expression of immune complement genes is an early event in glaucomatous damage. Complement activation leads to destruction of dendritic RGC synapses, resulting in RGC dysfunction and susceptibility. We thus hypothesize that complement inhibitors play a role in neuroprotection early in disease, but whether complement underlies development of primary open angle glaucoma (POAG) in humans remains unknown. Here, we test whether polymorphisms affecting complement inhibition are associated with primary open angle glaucoma (POAG) in Latinos.
Out of 290 POAG cases identified in LALES, a population-based study on the incidence/ prevalence of major eye diseases, we selected all cases with available DNA samples (172) as our case group. As controls, we selected 172 individuals with no eye disease (POAG, AMD, or diabetic retinopathy) from the LALES cohort by frequency matching to age, central corneal thickness, smoking and diabetes. We used TaqMan assays (ABI) to sequence a total of 10 single nucleotide polymorphisms (SNPs) across genes that activate or inhibit the complement cascade, namely Serping-1, C2, Factor B, C3, and CFH; sequencing was performed at USC’s epigenome center. The selected SNPs are predicted to change the expression or aminoacid code of the genes of interest. Chi square analysis and one-sided P values (5% significance level) were calculated to determine association of risk genotypes (either heterozygous or homozygous for the risk SNP) and POAG.
The frequency of risk genotypes (fRG) for rs2509897, a SNP in the promoter region of Serping-1 predicted to affect gene expression, was 31% higher in our POAG cases (50.3%) compared to controls (38.3%), p=0.02. The odds ratio of POAG conferred by this SNP was 1.6. Similarly, the fRG in C3 that result in the C3 fast variant (rs2231099, predicted to be an overactive form of C3) was modestly higher in POAG cases (19.8%) compared to controls (14.6%). Although this was not statistically significant (p=0.07), the odds ratio conferred by rs2231099 was also 1.6. There was also a trend for a higher fRG for rs1061170 (CFH Y402H) in cases of joint AMD and POAG compared to either control, AMD alone or POAG alone (p=0.07, OR=1.8 vs. control). We did not find an association between rs4926 (V480M in Serping-1), rs1047286 (P292L in C3), or polymorphisms in C2 or Factor B and POAG, although our sample was too small to detect differences in relatively rare polymorphisms.
Our preliminary analysis suggests that risk polymorphisms in complement regulators may be associated with POAG.
This PDF is available to Subscribers Only