Population-specific association between a polymorphic variant in ST18, encoding a pro-apoptotic molecule, and pemphigus vulgaris

Ofer Sarig, Sivan Bercovici, Lilach Zoller, Ilan Goldberg, Margarita Indelman, Sagi Nahum, Shirli Israeli, Nadav Sagiv, Helena Martinez De Morentin, Oren Katz, Sharon Baum, Aviv Barzilai, Henri Trau, Dedee F. Murrell, Reuven Bergman, Michael Hertl, Shai Rosenberg, Markus M. Nöthen, Karl Skorecki, Enno SchmidtDetlef Zillikens, Ariel Darvasi, Dan Geiger, Saharon Rosset, Saleh M. Ibrahim*, Eli Sprecher

*Corresponding author for this work
26 Citations (Scopus)


Pemphigus vulgaris (PV) is a severe autoimmune blistering disease caused by anti-epithelial antibodies, leading to disruption of cell-cell adhesion. Although the disease is exceedingly rare worldwide, it is known to be relatively prevalent in Jewish populations. The low prevalence of the disease represents a significant obstacle to a genome-wide approach to the mapping of susceptibility genes. We reasoned that the study of a genetically homogeneous cohort characterized by a high prevalence of PV may help exposing associated signals while reducing spurious results due to population sub-structure. We performed a genome-wide association study using 300K single-nucleotide polymorphisms (SNPs) in a case-control study of 100 PV patients of Jewish descent and 397 matched control individuals, followed by replication of significantly associated SNPs in three additional cohorts of Jewish, Egyptian, and German origin. In addition to the major histocompatibility complex locus, a genomic segment on 8q11.23 that spans the ST18 gene was also found to be significantly associated with PV. This association was confirmed in the Jewish and Egyptian replication sets but not in the German sample, suggesting that ST18-associated variants may predispose to PV in a population-specific manner. ST18 regulates apoptosis and inflammation, two processes of direct relevance to the pathogenesis of PV. Further supporting the relevance of ST18 to PV, we found this gene to be overexpressed in the skin of PV patients as compared with healthy individuals.

Original languageEnglish
JournalJournal of Investigative Dermatology
Issue number7
Pages (from-to)1798-1805
Number of pages8
Publication statusPublished - 01.07.2012


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