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法国人群体中6号染色体p21区域和20号染色体p13区域银屑病易感基因座的确认

Confirmation of psoriasis susceptibility loci on chromosome 6p21 and 20p13 in French families.

作者信息

Lesueur Fabienne, Lefèvre Caroline, Has Cristina, Guilloud-Bataille Michel, Oudot Tiphaine, Mahé Emmanuel, Lahfa Morad, Mansouri Samira, Mosharraf-Olmolk Haydeh, Sobel Eric, Heath Simon, Lathrop Mark, Dizier Marie-Hélène, Prud'Homme Jean-François, Fischer Judith

机构信息

Centre National de Génotypage, Evry, France.

出版信息

J Invest Dermatol. 2007 Jun;127(6):1403-9. doi: 10.1038/sj.jid.5700749. Epub 2007 Mar 8.

Abstract

Plaque psoriasis is a chronic inflammatory disorder of the skin. It is inherited as a multifactorial trait, with a strong genetic component. Linkage studies have identified a large number of disease loci, but very few could be replicated in independent family sets. In this study, we present the results of a genome-wide scan carried out in 14 French extended families. Candidate regions were then tested in a second set of 32 families. Analysis of the pooled samples confirmed linkage to chromosomes 6p21 (Z(MLB) score=3.5, P=0.0002) and 20p13 (Z(MLB) score=2.9, P=0.002), although there was little contribution of the second family set to the 20p13 linkage signal. Moreover, we identified four additional loci potentially linked to psoriasis. The major histocompatibility complex region on 6p21 is a major susceptibility locus, referred to as PSORS1, which has been found in most of the studies published to date. The 20p13 locus segregates independently of PSORS1 in psoriasis families. It has previously been thought to be involved in the predisposition to psoriasis and other inflammatory disorders such as atopic dermatitis (AD) and asthma. Although psoriasis and AD rarely occur together, this reinforces the hypothesis that psoriasis is influenced by genes with general effects on inflammation and immunity.

摘要

斑块状银屑病是一种慢性皮肤炎症性疾病。它作为一种多因素性状遗传,具有很强的遗传成分。连锁研究已经确定了大量的疾病基因座,但在独立的家系中很少能重复验证。在本研究中,我们展示了对14个法裔大家庭进行全基因组扫描的结果。然后在另外32个家庭中对候选区域进行了检测。对合并样本的分析证实与6号染色体p21区域(Z(MLB)评分 = 3.5,P = 0.0002)和20号染色体p13区域(Z(MLB)评分 = 2.9,P = 0.002)存在连锁关系,尽管第二个家系组对20p13连锁信号的贡献很小。此外,我们还确定了另外四个可能与银屑病相关的基因座。6号染色体p21上的主要组织相容性复合体区域是一个主要的易感基因座,称为PSORS1,在迄今为止发表的大多数研究中都已发现。在银屑病家系中,20p13基因座与PSORS1独立分离。以前人们认为它与银屑病以及其他炎症性疾病如特应性皮炎(AD)和哮喘的易感性有关。尽管银屑病和AD很少同时发生,但这强化了银屑病受对炎症和免疫有普遍影响的基因影响的假说。

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