Identification Of Genetic Risk Factors In Pigmentary Glaucoma
1. A regional cohort of 200 German pigmentary glaucoma patients will be analyzed by means of a direct mutation scanning. Changes in DNA caused by a mutation can cause errors in protein sequence, creating partially or completely non-functional proteins. We aim to identify such mutations in genes that were selected due to their role in several mouse strains that exhibit features which resemble the features in human pigmentary glaucoma. The direct mutation scanning enables to detect mutations in a single patient, however, due to methodological limitations, mutations can be missed sometimes.
2. The direct mutation scanning will therefore be complemented with the analyses of SNPs. A single nucleotide polymorphism (SNP, pronounced snip) is a DNA sequence variation occurring when a single nucleotide - A, T, C, or G - in the genome differs between members of a species. The analysis of SNPs can overcome the limitation of the direct mutation scanning technology when used in a case control study. Case-control is a type of epidemiological study design and is used to identify factors that may contribute to a disease by comparing subjects who have that condition (the 'cases') with patients who do not have the condition but are otherwise similar (the 'controls'). We will therefore compare our 200 patients with 280 healthy controls by analyzing many SNPs surrounding the abovementioned genes. Differences in the frequency of these SNPs between the two groups may indicate that the genetic marker increases the risk of developing pigmentary glaucoma.
While the direct mutation screening approach favors the individual, a case control study is a type of epidemiological study (i.e. the study of factors affecting the health and illness of populations) designed to define a relative risk of a group. We will use well-characterized groups of people with and without pigmentary glaucoma, and compare common variation(s) in a range of candidate genes in both groups. If the majority of cases with pigmentary glaucoma are due to the combined effects of multiple genetic variants, this will be a more powerful approach to identify genetic risk factors that affect the likelihood of developing glaucoma.
Panidou, E., Wolf, C., Gramer, G., Weisschuh, N., Fischer, D., Wissinger, B. and Gramer, E. (2010) Role of central corneal thickness in pigmentary glaucoma [PMID:nd:[link not available]
(Our results indicate that PG patients with thinner corneas are just as likely to have advanced levels of visual field loss as PG patients with thicker corneas. This separates PG from primary open angle glaucoma, where thinner central corneal thickness has been identified previously as a strong predictive factor.)
Gramer, E., Panodou, E., Gramer, G., Weisschuh, N., Fischer, D., Wissinger, B., Wolf, C. (2010) Intraocular pressure is correlated with age at diagnosis and visual field loss in patients with pigmentary glaucoma [PMID:nd:[link not available]
(We could show that higher intraocular pressure leads to a significant earlier diagnosis of PG. In addition, we observed a significant association between a positive family history and intraocular pressure.)
First published on: April 14, 2009
Last modified on: August 20, 2010