Linkage Analysis in Keratoconus: Replication of Locus 5q21.2 and Identification of Other Suggestive Loci
Linkage Analysis in Keratoconus: Replication of Locus 5q21.2 and Identification of Other Suggestive Loci
复制标题
DOI：
10.1167/iovs.08-2382
复制
发表时间：
2009-03-01
影响因子：
4.4
通讯作者：
Zelante, Leopoldo
中科院分区：
文献类型：
--
作者：
Bisceglia, Luigi;De Bonis, Patrizia;Zelante, Leopoldo
目的。圆锥角膜（KC）是西方世界最常见的角膜移植适应症，其病因机制尚不清楚。该病在一般人群中的患病率约为1:2000，家族聚集性以及家族风险的增加表明其发病机制受到重要的遗传影响。迄今为止，已经描述了几个家族性圆锥角膜的基因座，但在各自的定位间隔中没有发现任何负责任的基因。本研究的目的是鉴定圆锥角膜的致病/易感基因。来自意大利南部25个家庭的133人（77人受影响，59人未受影响）使用微卫星标记进行基因分型，并纳入全基因组扫描。利用遗传算法软件计算非参数分析和参数分析，采用只受影响策略。非参数分析显示，5q32-q33、5q21.2、14q11.2、15q2.32染色体区域显示出最强的连锁证据（NPL分别为3.22、2.73、2.62和2.32）。5q32-q33和14q11.2区域的异质性LOD （HLOD）得分分别为2.45 （alpha = 0.54）和2.09 （alpha = 0.46）。该研究首次对染色体区域5q21.2进行了KC连锁复制研究，并报告了在几个区域存在暗示连锁的证据，这些区域之前在不同人群中检测到暗示或显著连锁。（中国眼科杂志，2009;50:1081-1086）DOI: 10.1167/iovs.08-2382
PURPOSE. Keratoconus (KC) is the most common indication for corneal transplantation in the Western world, with etiologic mechanisms still poorly understood. The disease prevalence in the general population is approximately 1:2000, and familial aggregation, together with increased familial risk, suggests important genetic influences on its pathogenesis. To date, several loci for familial keratoconus have been described, without the identification of any responsible gene in the respective mapped intervals. The aim of this study was to identify causative/susceptibility genes for keratoconus.METHODS. A total of 133 individuals (77 affected and 59 unaffected) of 25 families from southern Italy were genotyped using microsatellite markers and included in a genome-wide scan. Nonparametric and parametric analysis using an affected-only strategy were calculated by using genetic algorithm software.RESULTS. The chromosomal regions 5q32-q33, 5q21.2, 14q11.2, 15q2.32 exhibited the strongest evidence of linkage by nonparametric analysis (NPL = 3.22, 2.73, 2.62, and 2.32, respectively). The regions 5q32-q33 and 14q11.2 were also supported by multipoint parametric analysis, for which heterogeneity LOD (HLOD) scores of 2.45 (alpha = 0.54) and 2.09 (alpha = 0.46), respectively, were obtained under an affected-only dominant model.CONCLUSIONS. This study represents the first KC linkage replication study on the chromosomal region 5q21.2 and reports evidence of suggestive linkage in several regions for which suggestive or significant linkage has been previously detected in different populations. (Invest Ophthalmol Vis Sci. 2009; 50: 1081-1086) DOI: 10.1167/iovs.08-2382