Recent progress in the genetics of Wegener's granulomatosis and Churg-Strauss syndrome

Curr Opin Rheumatol. 2010 Jan;22(1):8-14. doi: 10.1097/BOR.0b013e3283331151.


Purpose of review: Recently, numerous studies have been performed to elucidate the genetic background of Wegener's granulomatosis and Churg-Strauss syndrome (CSS). Many of these investigations suffer from low statistical power, inconsistent case classification and other error-prone study designs. The majority of these findings has to be considered preliminary, if not spurious. We summarize the most important and robust findings.

Recent findings: HLA-DPB1, the association of which with Wegener's granulomatosis has been discovered some years ago, is still the strongest and best replicated risk locus for this condition. Yet, no association is demonstrable for CSS, in which another HLA locus, HLA-DR, seems to be more important. Vice versa, a strong association with IL10 promotor polymorphisms was detected in CSS but not in a large Wegener's granulomatosis panel. Numerous other associations, including CTLA4, CD226 and copy number polymorphisms of FCGR3B still need further investigation, before reliable conclusions can be drawn.

Summary: In order to be able to evaluate critically the genetic background of Wegener's granulomatosis and CSS future projects should take into account several aspects of study design. These preconditions include sufficient numbers of cases (i.e. statistical power) and a clear-cut classification of these cases, thus allowing differentiated analyses of certain disease subgroups.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Churg-Strauss Syndrome / genetics*
  • Churg-Strauss Syndrome / immunology
  • Churg-Strauss Syndrome / physiopathology
  • Genetic Association Studies / standards
  • Genetic Association Studies / statistics & numerical data
  • Genetic Association Studies / trends
  • Genetic Predisposition to Disease / genetics*
  • Granulomatosis with Polyangiitis / genetics*
  • Granulomatosis with Polyangiitis / immunology
  • Granulomatosis with Polyangiitis / physiopathology
  • HLA Antigens / genetics*
  • HLA-DP Antigens / genetics
  • HLA-DP beta-Chains
  • HLA-DR Antigens / genetics
  • Humans
  • Interleukin-10 / genetics
  • Polymorphism, Genetic / genetics*


  • HLA Antigens
  • HLA-DP Antigens
  • HLA-DP beta-Chains
  • HLA-DPB1 antigen
  • HLA-DR Antigens
  • Interleukin-10