Charlesworth Jac C, Dyer Thomas D, Stankovich Jim M, Blangero John, Mackey David A, Craig Jamie E, Green Catherine M, Foote Simon J, Baird Paul N, Sale Michèle M
Menzies Research Institute, University of Tasmania, Hobart, Australia.
Invest Ophthalmol Vis Sci. 2005 Oct;46(10):3723-9. doi: 10.1167/iovs.05-0312.
The purpose of this study was to identify genetic contributions to primary open-angle glaucoma (POAG) through investigations of two quantitative components of the POAG phenotype.
Genome-wide multipoint variance-components linkage analyses of maximum recorded intraocular pressure (IOP) and maximum vertical cup-to-disc ratio were conducted on data from a single, large Australian POAG pedigree that has been found to segregate the myocilin Q368X mutation in some individuals.
Multipoint linkage analysis of maximum recorded IOP produced a peak LOD score of 3.3 (P = 0.00015) near marker D10S537 on 10q22, whereas the maximum cup-to-disc ratio produced a peak LOD score of 2.3 (P = 0.00056) near markers D1S197 to D1S220 on 1p32. Inclusion of the myocilin Q368X mutation as a covariate provided evidence of an interaction between this mutation and the IOP and cup-to-disc ratio loci.
Significant linkage has been identified for maximum IOP and suggestive linkage for vertical cup-to-disc ratio. Identification of genes contributing to the variance of these traits will enhance understanding of the pathophysiology of POAG as a whole.
本研究的目的是通过对原发性开角型青光眼（POAG）表型的两个定量成分进行调查，确定其遗传贡献。
对来自一个大型澳大利亚POAG家系的数据进行全基因组多点方差成分连锁分析，该家系部分个体存在肌纤蛋白Q368X突变，分析指标为最大记录眼压（IOP）和最大垂直杯盘比。
最大记录眼压的多点连锁分析在10q22的标记D10S537附近产生了一个峰值LOD分数3.3（P = 0.00015），而最大杯盘比在1p32的标记D1S197至D1S220附近产生了一个峰值LOD分数2.3（P = 0.00056）。将肌纤蛋白Q368X突变作为协变量纳入分析，提供了该突变与眼压及杯盘比位点之间存在相互作用的证据。
已确定最大眼压存在显著连锁，垂直杯盘比存在提示性连锁。确定导致这些性状变异的基因将增强对整个POAG病理生理学的理解。
