Abstract

We investigated the potential association between cyclooxygenase-2 (COX-2) gene polymorphisms and clinical manifestations of sarcoidosis. This observational cross-sectional study involved seven hospitals in Spain. We diagnosed patients with sarcoidosis according to the International Criteria. The following 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. nonsystemic. Genotyping of four COX-2 polymorphisms (COX2.5909T>G, COX2.8473T>C, COX2.926G>C, and COX2.3050G>C) was undertaken on DNA extracted from peripheral blood lymphocytes using fluorescent hybridization probes and melting curves. A total of 131 sarcoid patients (63 males, mean age: 47 +/- 15 years) were studied. One hundred twenty-six of these patients had one or more positive biopsies. The results demonstrated that genotype distribution for the COX2.3050G>C polymorphism was significantly different between patients with systemic sarcoidosis and those with nonsystemic forms (p = 0.046). After adjustment for age, gender, and serum ACE levels, a significant association between the carriage of at least one C allele of the COX2.3050G>C polymorphism and systemic sarcoidosis was observed (odds ratio [OR]: 2.3; 95% confidence interval [CI]: 1.03-5.12, p = 0.031). Other polymorphisms were not associated with either clinical manifestations of the disease or serum ACE levels. Our results indicate for the first time that the C allele of the COX2.3050G>C polymorphism is associated with systemic sarcoidosis.

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