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.
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.
Authors: Isham Huizar; Anagha Malur; Yasmeen A Midgette; Cindy Kukoly; Pengyu Chen; Pu Chun Ke; Ramakrishna Podila; Apparao M Rao; Christopher J Wingard; Larry Dobbs; Barbara P Barna; Mani S Kavuru; Mary Jane Thomassen Journal: Am J Respir Cell Mol Biol Date: 2011-03-11 Impact factor: 6.914
Authors: Paul A Lyons; Tim F Rayner; Sapna Trivedi; Julia U Holle; Richard A Watts; David R W Jayne; Bo Baslund; Paul Brenchley; Annette Bruchfeld; Afzal N Chaudhry; Jan Willem Cohen Tervaert; Panos Deloukas; Conleth Feighery; Wolfgang L Gross; Loic Guillevin; Iva Gunnarsson; Lorraine Harper; Zdenka Hrušková; Mark A Little; Davide Martorana; Thomas Neumann; Sophie Ohlsson; Sandosh Padmanabhan; Charles D Pusey; Alan D Salama; Jan-Stephan F Sanders; Caroline O Savage; Mårten Segelmark; Coen A Stegeman; Vladimir Tesař; Augusto Vaglio; Stefan Wieczorek; Benjamin Wilde; Jochen Zwerina; Andrew J Rees; David G Clayton; Kenneth G C Smith Journal: N Engl J Med Date: 2012-07-19 Impact factor: 91.245
Authors: Michelle M A Fernando; Jan Freudenberg; Annette Lee; David Lester Morris; Lora Boteva; Benjamin Rhodes; María Francisca Gonzalez-Escribano; Miguel Angel Lopez-Nevot; Sandra V Navarra; Peter K Gregersen; Javier Martin; Timothy J Vyse Journal: Ann Rheum Dis Date: 2012-01-10 Impact factor: 19.103
Authors: Janet Wohlers; Katrin Breucker; Rainer Podschun; Jürgen Hedderich; Peter Lamprecht; Petra Ambrosch; Martin Laudien Journal: Arthritis Res Ther Date: 2012-10-17 Impact factor: 5.156