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A. S. Hoguet, E. DelBono, R. R. Allingham, M. Pericak-Vance, M. A. Hauser, J. L. Haines, J. L. Wiggs; GLC1K Is Associated With Early-Onset and Late-Onset Primary Open Angle Glaucoma. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5601.
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We have previously identified a locus on chromosome 20 (GLC1K) for early onset primary open angle glaucoma (JOAG). Further genome studies using 5,067 SNPs also demonstrated suggestive linkage to this region in a set of 86 families affected by adult-onset primary open angle glaucoma (LOD > 2.0). The purpose of this study is to perform association analyses using single nucleotide polymorphisms distributed throughout this region to identify and evaluate candidate genes for JOAG and POAG.
238 POAG patients (67.6% Caucasian, 25.6% African, 6.7% Other) and 112 controls (87.5% Caucasian, 7.1% African, 5.4% Other) were used for the case/control association analysis. A large JOAG pedigree with evidence of linkage to GLC1K (14 members) was used to initially delineate a region of linkage on chromosome 20. 25 SNPs distributed throughout the region were then evaluated for association in the POAG case/control cohort using a quantitative PCR approach (TaqMan assay) by calculating a chi square distribution for genotype and allele frequency.
SNPs rs714235 (chr20:11538160bp) and rs6041429 (chr20:12455646 bp) show significant association with POAG for genotype (p=5.2x10-4 and p= 2.0x10-4 respectively) and allele frequency (p=0.07 and p=7.8x10-5 respectively). The BTBD3 gene (chr20: 118194977) is located between these SNPs and was screened for DNA sequence variants by PCR amplification followed by direct genomic sequencing. Biologically significant DNA sequence variants in this gene were not identified in JOAG patients, and further evaluation in POAG patients is ongoing.
This study shows that the GLC1K region may be associated with both early onset and late onset primary open angle glaucoma. Linkage studies had previously identified a 19cM region containing a number of possible candidate genes. Association studies have shown significant association between POAG and SNPs rs714235 and rs6041429. Further association analyses with additional SNPs and evaluation of candidate genes in the region of association is currently underway.
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