Purchase this article with an account.
Y. Liu, S. Schmidt, X. Qin, D. Munro, J. Gibson, K. Hutchins, K. LaRocque-Abramson, C. Santiago-Turla, R. R. Allingham, M. A. Hauser; Significant Association Between Dynamin-Binding Protein and Primary Open-Angle Glaucoma in the Caucasian Population. Invest. Ophthalmol. Vis. Sci. 2009;50(13):881.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Currently, gene variants known to be associated with primary open-angle glaucoma (POAG) explain only a small proportion of the disease. The goal of our study is to identify additional POAG susceptibility genes.
We performed a linkage analysis of 124 multiplex POAG families using the Illumina linkage IV SNP panel. We evaluated genomic regions with multiple clustered two-point lod scores for the presence of functional candidate genes from POAG-relevant pathways. One such region included the gene encoding Dynamin-binding protein (DNMBP). Thirteen tagging SNPs in this gene were tested for association with POAG in our Caucasian, African American, and Ghanaian case-control datasets.
SNPs rs11190305, rs7903096, and rs12764325 showed a significant association with POAG risk (p=0.004, 0.004, and 0.002 respectively) in the Caucasian dataset of 330 POAG cases and 360 controls. Rs11190305 is a non-synonymous coding SNP that induces a change from Cys(C) to Trp(W) at amino acid 1413 in DNMBP. Ordered subset analysis using age at onset provided significantly increased evidence for association in a subset of 156 POAG patients with onset below 57 years of age (permutation test p-value 0.001). In this subset of patients, the G allele at rs11190305 (Trp1413) had a frequency of 47%, compared to 35% in controls (p = 0.00015). No significant association with C1413W was found in either our African American or Ghanaian datasets.
Some investigators have suggested similarities between the pathogenesis of Alzheimer’s disease (AD) and POAG. DNMBP has been associated with late-onset AD in Japanese and Belgian populations. DNMBP is a scaffold protein that brings the dynamin and actin regulatory proteins together, and is concentrated at synapses. This is the first report of a significant association of coding variant C1413W in DNMBP with an increased risk of POAG in Caucasians but not in our African American or Ghanaian (West African) datasets. Our analysis suggests that the association may be stronger in a subset of patients with early age at onset.
This PDF is available to Subscribers Only