PT - JOURNAL ARTICLE AU - H. Sato AU - H. R. T. Williams AU - P. Spagnolo AU - A. Abdallah AU - T. Ahmad AU - T. R. Orchard AU - S. J. Copley AU - S. R. Desai AU - A. U. Wells AU - R. M. du Bois AU - K. I. Welsh TI - <em>CARD15/NOD2</em> polymorphisms are associated with severe pulmonary sarcoidosis AID - 10.1183/09031936.00010209 DP - 2010 Feb 01 TA - European Respiratory Journal PG - 324--330 VI - 35 IP - 2 4099 - http://erj.ersjournals.com/content/35/2/324.short 4100 - http://erj.ersjournals.com/content/35/2/324.full SO - Eur Respir J2010 Feb 01; 35 AB - Sarcoidosis and Crohn’s disease are heterogeneous systemic diseases characterised by granulomatous inflammation. Caspase recruitment domain (CARD)15 is a major susceptibility gene for Crohn’s disease, and specifically for ileal and fibrostenotic subtypes. The C-C chemokine receptor (CCR)5 gene has been associated with both parenchymal pulmonary sarcoidosis and perianal Crohn’s disease. This study explored associations between CARD15 polymorphisms, CCR5 haplotype and distinct pulmonary sarcoidosis subtypes. 185 Caucasian sarcoidosis patients were genotyped for CARD15 and CCR5 polymorphisms. The genetic data were compared with 347 healthy controls and were examined for associations with serial pulmonary function tests and chest radiographs. CARD15 genotypes did not differ between the unselected sarcoidosis cohort and controls. However, patients carrying the functional 2104T (702W) polymorphism were more likely to have radiographic stage IV disease at 4-yr follow-up. All patients possessing both CARD15 2104T and CCR5 HHC haplotype had stage IV disease at presentation. Carriage of 2104T was associated with worse forced expiratory volume in 1 s, whereas carriage of the CARD15 1761G (587R) polymorphism was associated with better lung function. For the first time, an association between two CARD15 polymorphisms and specific sarcoidosis phenotypes has been demonstrated, as well as an additive effect of possessing CARD15 2104T and CCR5 HHC haplotype.