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Abstract #46764 Published in IGR 13-3
Genome-wide association study with DNA pooling identifies variants at CNTNAP2 associated with pseudoexfoliation syndrome and pseu-doexfoliation glaucoma
Krumbiegel M; Pasutto F; Schlotzer-Schrehardt U; Uebe S; Zenkel M; Mardin CY; Weisschuh N; Paoli D; Gramer E; Becker CMedizinische Genetik 2010; 22: 131
PURPOSE: Genetic and non-genetic factors contribute to the development of pseudoexfoliation (PEX) syndrome, a complex, age-related, generalized matrix process which is mainly manifest in eyes and frequently associated with glaucoma. In order to identify specific genetic variants underlying its aetiology, we performed a genome-wide association study (GWAS) using DNA pooling approach. METHODS: Equimolar amounts of DNA samples of 80 subjects with PEX syndrome, 80 with PEX glaucoma and 80 controls, respectively, were combined into three separate pools and hybridized to 500K SNP arrays (Affymetrix). Array probe intensity data was analyzed and visualized with specially developed software tools GPFrontend and GPGraphics in combination with the GenePool program. For replication, independent German cohorts of 6i0 unrelated patients with PEX/ PEXG and 364 controls as well as Italian cohorts of 249 patients and 190 controls were used. RESULTS: Genotyping of selected SNPs in the CNTNAP2 locus revealed significant association between PEX/PEXG and two SNPs as well as their haplotype. The association found was confirmed in an independent German cohort but not in an Italian cohort. In the combined German cohorts the two SNPs remained significant after correction with permutation test (rs2107856: Pc=0.0044, rs2141388: Pc=0.0029). Ubiquitously expression pattern in human ocular tissues and a clearly localization to cell membranes of epithelial, endothelial, smooth muscle, glial and neuronal cells revealed CNTNAP2 protein as an interesting candidate for PEX disease. CONCLUSION: Confirming efficiency of GWAS with DNA pooling approach, our data show compelling evidence for the association of CNTNAP2 with PEX syndrome and PEXG in German patients.
M. Krumbiegel. Institute of Human Genetics, Erlangen, Germany.
Classification:
9.4.4.1 Exfoliation syndrome (Part of: 9 Clinical forms of glaucomas > 9.4 Glaucomas associated with other ocular and systemic disorders > 9.4.4 Glaucomas associated with disorders of the lens)
3.4.1 Linkage studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)
