Winsey Samantha, Lonie Lorne, Allen Jill, Bunce Mike, Marshall Sara E, Wojnarowska Fenella
Department of Dermatology, University of Oxford, Churchill Hospital, Oxford, UK.
Exp Dermatol. 2004 Mar;13(3):140-7. doi: 10.1111/j.0906-6705.2004.0138.x.
Bullous pemphigoid (BP) is an autoimmune blistering disease of the skin characterized by autoantibody attack on collagen XVII.
To characterize the genetic complexity of COL17A1, the gene which encodes for the autoantigen collagen XVII. The data will be used to determine whether there is an association between polymorphisms and haplotypes of COL17A1 and genetic susceptibility to development of BP.
The genetic complexity in COL17A1 was deduced by screening and then sequencing the gene. Haplotypes were constructed from the resulting polymorphisms using the statistical programme PHASE. The linkage disequilibrium (D') between the polymorphisms was deduced from haplotypic data using the statistical programme GOLD. Association of the polymorphisms and haplotypes was tested for, in a cohort of BP patients and controls.
Screening of COL17A1 for genetic variation was carried out in 29 individuals of North European caucasoid origin, and it revealed 19 single-nucleotide polymorphisms in approximately 14.7 kb of sequence. These variants resulted in 60 different haplotypes in 191 individuals, of which 13 occurred above 1% in the population. D' between the variants was found to be extensive, have a low correlation with physical distance and to extend over 33.8 kb. No association was found with any of the polymorphisms or haplotypes and development of BP, when tested for, in a cohort of patients and controls.
This study provides an extensive description of the genetic variation in COL17A1 and shows no association of the genetic variants with susceptibility to BP.
大疱性类天疱疮（BP）是一种皮肤自身免疫性水疱病，其特征是自身抗体攻击ⅩⅦ型胶原蛋白。
描述编码自身抗原ⅩⅦ型胶原蛋白的COL17A1基因的遗传复杂性。这些数据将用于确定COL17A1基因的多态性和单倍型与BP发病的遗传易感性之间是否存在关联。
通过筛选然后对该基因进行测序来推断COL17A1基因的遗传复杂性。使用统计程序PHASE从所得的多态性构建单倍型。使用统计程序GOLD从单倍型数据推断多态性之间的连锁不平衡（D'）。在一组BP患者和对照中测试多态性和单倍型的关联性。
对29名北欧白种人起源的个体进行了COL17A1基因变异的筛选，在大约14.7kb的序列中发现了19个单核苷酸多态性。这些变异在191名个体中产生了60种不同的单倍型，其中13种在人群中的出现频率高于1%。发现这些变异之间的D'广泛，与物理距离的相关性低，并且延伸超过33.8kb。在一组患者和对照中进行测试时，未发现任何多态性或单倍型与BP发病之间存在关联。
本研究对COL17A1基因的遗传变异进行了广泛描述，表明这些遗传变异与BP易感性无关。
