King's College London

Research portal

Genomewide association study identifies GALC as susceptibility gene for mucous membrane pemphigoid

Research output: Contribution to journalArticle

Christian D. Sadik, Julia Bischof, Nina Van Beek, Anabelle Dieterich, Sandrine Benoit, Miklós Sárdy, Margitta Worm, Stephan Meller, Regine Gläser, Detlef Zillikens, Bernhard Homey, Jane Setterfield, Darwin Minassian, Enno Schmidt, John Dart, Saleh M. Ibrahim

Original languageEnglish
Pages (from-to)1214-1220
JournalExperimental Dermatology
Issue number12
Early online date27 Dec 2017
Publication statusE-pub ahead of print - 27 Dec 2017


King's Authors


Mucous membrane pemphigoid (MMP) is a rare, chronic and often aggressive subepidermal autoimmune blistering disease potentially affecting several mucous membranes with blisters and secondary erosions and scars. The pathogenesis of MMP is poorly understood, and the contribution of genetic predispositions, other than HLA class II allele variants to MMP, is unknown. The objective of this study is to identify susceptibility genes for MMP in a British cohort of MMP patients. A GWAS was conducted in a British cohort of 106 MMP patients. Publicly available genotypes of 2900 blood donors of the UK Blood Service and of 6740 individuals of the 1958 British Birth Cohort served as control. Subsequently, putative susceptibility genes were independently replicated in a German cohort of 42 MMP patients. The GWAS found 38 SNPs in 28 haploblocks with an odds ratio >2 reaching genomewide significance (P < 5.7 × 10−7). Replication confirmed an association of MMP with SNPs in rs17203398 (OR: 3.9), located intronically in the β-galactocerebrosidase gene (GALC) on chromosome 14 and with recessive polymorphisms in rs9936045 (OR: 3.1) in the intergenic region between CASC16 and CHD9 on chromosome 16. The risk of developing MMP is partially genetically determined. SNPs in GALC enhance the risk for MMP, indicating that β-galactocerebrosidase may be involved in the pathogenesis of MMP. Likewise, impacts of polymorphisms in the intergenic region between CASC16 and CHD9 on the activity of neighbouring genes may facilitate the emergence of MMP. The putative role of both polymorphisms requires functional studies in the future.

Download statistics

No data available

View graph of relations

© 2018 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454