Corneodesmosin (CDSN) gene association with psoriasis vulgaris in Caucasian but not in Japanese populations
Corneodesmosin (CDSN) gene association with psoriasis vulgaris in Caucasian but not in Japanese populations
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DOI：
10.1111/j.1365-2230.2005.01789.x
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发表时间：
2005-07-01
影响因子：
4.1
通讯作者：
Barker, JNWN
中科院分区：
文献类型：
--
作者：
Ameen, M;Allen, MH;Barker, JNWN
染色体6p21.3上含有MHC的PSORS 1是寻常型银屑病的主要易感位点。该区域的特征在于强烈的连锁不平衡，并包含corneodesmosin（CSDN）基因，一个有吸引力的候选人银屑病易感性的基础上，其推定的生物学功能角质细胞粘附，和HLA-Cw 6，银屑病易感性的一个既定的标志物。我们比较了两个遗传上独立的人群，以确定主要的银屑病易感基因，一个英国白人人口包括父母-后代三人组分析的传播不平衡检验（TDT）和日本的病例对照人群。所有受试者均进行CDSN多态性（+619、+1236、+1240和+1243）和HLA-C相关性研究。我们的数据证实了在高加索人群中HLA-Cw 6和CDSN等位基因5（+619 T，+1240 G，+1243 C）的强相关性（TDT，P = 5.4 x 10（-6）），此外通过鉴定高风险CDSN单倍型（等位基因5和+1236 T，P = 8.5 x 10（-8））进一步定义了该区域。相反，在日本队列中没有观察到任何HLA-C或CDSN等位基因的相关性。这一数据支持CDSN基因在高加索人群银屑病中的作用。然而，在日本银屑病患者中缺乏与HLA-Cw 6和CDSN等位基因的相关性可能是因为日本患者表现出与晚发型或11型寻常型银屑病相似的银屑病形式，而与我们的高加索人群的早发或I型疾病特征相反。
PSORS1 on chromosome 6p21.3, which contains the MHC, is a major susceptibility locus for psoriasis vulgaris. This region is characterized by strong linkage disequilibrium and contains the corneodesmosin (CSDN) gene, an attractive candidate for psoriasis susceptibility based on its putative biological function in keratinocyte adhesion, and HLA-Cw6, an established marker for psoriasis susceptibility. We compared two genetically independent populations in order to define the major psoriasis susceptibility gene, a British Caucasian population comprising parent-offspring trios analysed by the transmission disequilibrium test (TDT) and a Japanese case-control population. All individuals were investigated for CDSN polymorphism (+619, +1236, +1240 and +1243) and HLA-C association. Our data confirms strong association with HLA-Cw6 and CDSN allele 5 (+619T, +1240G, +1243C) in the Caucasian cohort (TDT, P = 5.4 x 10(-6)) and in addition defines this region further by identifying a high-risk CDSN haplotype (allele 5 and +1236T, P = 8.5 x 10(-8)). In contrast no association was observed in the Japanese cohort for any HLA-C or CDSN alleles. This data supports a role for the CDSN gene in Caucasian populations with psoriasis. However the lack of association with HLA-Cw6 and CDSN alleles in Japanese psoriasis patients may be because Japanese patients exhibit a form of psoriasis similar to late onset or Type 11 psoriasis vulgaris in contrast to early onset or Type I disease characterizing our Caucasian population.