Background: Bullous pemphigoid (BP) is an autoimmune blistering disease of the skin characterized by autoantibody attack on collagen XVII.
Objectives: 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.
Methods: 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.
Results: 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.
Conclusion: This study provides an extensive description of the genetic variation in COL17A1 and shows no association of the genetic variants with susceptibility to BP.