Karason Ari, Gudjonsson Johann E, Upmanyu Ruchi, Antonsdottir Arna A, Hauksson Valdimar B, Runasdottir E Hjaltey, Jonsson Hjortur H, Gudbjartsson Daniel F, Frigge Michael L, Kong Augustine, Stefansson Kari, Valdimarsson Helgi, Gulcher Jeffrey R
deCODE Genetics, Reykjavik, Iceland.
Am J Hum Genet. 2003 Jan;72(1):125-31. doi: 10.1086/345646. Epub 2002 Dec 9.
Several genetic loci have been reported for psoriasis, but none has been specifically linked to psoriatic arthritis (PsA), a condition that affects >10% of patients with psoriasis. A genetic component for PsA is suggested by segregation within families and high concordance among identical twins. We performed a linkage scan to map genes contributing to PsA. We identified 178 patients with PsA out of 906 patients who were included in our genetic study of psoriasis. Using a comprehensive genealogy database, we were able to connect 100 of these into 39 families. We genotyped the patients using a framework marker set of 1,000 microsatellite markers, with an average density of 3 cM, and performed multipoint, affected-only, allele-sharing linkage analysis using the Allegro program. On the basis of the initial results, we genotyped more markers for the most prominent loci. A linkage with a LOD score of 2.17 was observed on chromosome 16q. The linkage analysis, conditioned on paternal transmission to affected individuals, gave a LOD score of 4.19, whereas a LOD score of only 1.03 was observed when conditioned for maternal transmission. A suggestive locus on chromosome 16q has previously been implicated in psoriasis. Our data indicate that a gene at this locus may be involved in paternal transmission of PsA.
已有多个与银屑病相关的基因位点被报道，但尚无一个基因位点与银屑病关节炎（PsA）有特异性关联，PsA在超过10%的银屑病患者中出现。PsA的遗传因素通过家族内分离现象以及同卵双胞胎间的高一致性得以体现。我们进行了一项连锁扫描以定位导致PsA的基因。在纳入银屑病基因研究的906例患者中，我们识别出178例PsA患者。利用一个全面的系谱数据库，我们能够将其中100例患者归入39个家族。我们使用一套由1000个微卫星标记组成的框架标记集对患者进行基因分型，平均密度为3厘摩（cM），并使用Allegro程序进行多点、仅针对受累个体的等位基因共享连锁分析。基于初步结果，我们对最显著的位点进行了更多标记的基因分型。在16号染色体长臂（16q）上观察到一个对数优势分数（LOD）为2.17的连锁。以父系传递给受累个体为条件的连锁分析给出的LOD分数为4.19，而以母系传递为条件时观察到的LOD分数仅为1.03。此前曾有一个位于16q染色体上的提示性位点与银屑病有关。我们的数据表明，该位点的一个基因可能参与了PsA的父系传递。
