ORIGINAL ARTICLE Association of the 3050GOC Polymorphism in the Cyclooxygenase 2 Gene with Systemic Sarcoidosis Jose ´ Luis Lopez-Campos, a D. Rodriguez-Rodriguez, a E. Rodriguez-Becerra, a I. Alfageme Michavila, b J. Fernandez Guerra, c F.J. Garcı ´a Hernandez, d A. Casanova, e J. Ferna ´ndez de Co ´rdoba Gamero, f A. Romero Ortiz, g E. Arellano-Orden, a and A. Montes-Worboys a a Unidad Me ´dico-Quiru ´rgica de Enfermedades Respiratorias, Hospital Universitario Virgen del Rocı ´o, Seville, Spain b Servicio de Neumologı ´a, Hospital Universitario de Valme, Seville, Spain c Seccio ´n de Neumologı ´a, Hospital Costa del Sol, Marbella, Ma ´laga, Spain d Unidad de Colagenosis, Hospital Universitario Virgen del Rocı ´o, Seville, Spain e Servicio de Neumologı ´a, Hospital Universitario de la Princesa, Madrid, Spain f Servicio de Neumologı ´a, Hospital Juan Ramo ´n Jime ´nez, Huelva, Spain g Servicio de Neumologı ´a, Hospital Universitario Virgen de las Nieves, Granada, Spain Received for publication October 31, 2007; accepted March 24, 2008 (ARCMED-D-07-00517). Published previously online April 28, 2008. Background. We investigated the potential association between cyclooxygenase-2 (COX- 2) gene polymorphisms and clinical manifestations of sarcoidosis. Methods. This observational cross-sectional study involved seven hospitals in Spain. We diagnosed patients with sarcoidosis according to the International Criteria. The fol- lowing variables were recorded: age, gender, initial diagnostic methods, serum angiotensin- converting enzyme (ACE) levels, pulmonary function tests, radiological stage, and clinical findings at diagnosis. Manifestations of sarcoidosis were classified as systemic vs. nonsys- temic. Genotyping of four COX-2 polymorphisms (COX2.5909TOG, COX2.8473TOC, COX2.926GOC, and COX2.3050GOC) was undertaken on DNA extracted from periph- eral blood lymphocytes using fluorescent hybridization probes and melting curves. Results. A total of 131 sarcoid patients (63 males, mean age: 47  15 years) were stud- ied. One hundred twenty-six of these patients had one or more positive biopsies. The re- sults demonstrated that genotype distribution for the COX2.3050GOC polymorphism was significantly different between patients with systemic sarcoidosis and those with non- systemic forms ( p 5 0.046). After adjustment for age, gender, and serum ACE levels, a sig- nificant association between the carriage of at least one C allele of the COX2.3050GOC polymorphism and systemic sarcoidosis was observed (odds ratio [OR]: 2.3; 95% confi- dence interval [CI]: 1.03e5.12, p 5 0.031). Other polymorphisms were not associated with either clinical manifestations of the disease or serum ACE levels. Conclusions. Our results indicate for the first time that the C allele of the COX2.3050GOC polymorphism is associated with systemic sarcoidosis. Ó 2008 IMSS. Published by Elsevier Inc. Key Words: Sarcoidosis, Clinical presentation, Cyclooxygenase-2, Polymorphisms. Introduction Sarcoidosis is a multisystem disorder that affects the lungs in 90% of the cases. It is characterized by T-cell and mono- nuclear phagocyte infiltration of affected organs, granuloma formation, and distortion of the normal microarchitecture (1). The condition usually presents in adults !40 years, most frequently between 20 and 29 years of age. It is slightly more predominant in women than in men, with an annual age-adjusted incidence rate in the U.S. of 35.5 cases/100,000 blacks and 10.9 cases/100,000 whites (2). In Spain, lower annual rates have been reported (3,4). In Address reprint requests to: Jose ´ Luis Lo ´pez-Campos, Unidad Me ´dico- Quiru ´rgica de Enfermedades Respiratorias, Hospital Universitario Virgen del Rocı ´o, Edif. Laboratorios, planta baja, Avda. Manuel Siurot, s/n. 41013 Seville, Spain; E-mail: lcampos@separ.es 0188-4409/08 $esee front matter. Copyright Ó 2008 IMSS. Published by Elsevier Inc. doi: 10.1016/j.arcmed.2008.03.004 Archives of Medical Research 39 (2008) 525e530