The Gene Polymorphism of Tumor Necrosis Factor-β, But Not That of Tumor Necrosis Factor-α, Is Associated With the Prognosis of Sarcoidosis

摘要

Objectives: Few genetic markers for the prognosis of sarcoidosis have been found. Tumornnecrosis factor (TNF)-a has been implicated in the pathogenesis of sarcoidosis. Induced TNF-anor TNF-b levels have been shown to be associated with the polymorphisms of the TNF genes. Weninvestigated the roles of such polymorphisms in the development and prolongation of sarcoidosis.nSubjects and measurements: One hundred ten Japanese patients with sarcoidosis and 161 con-ntrol subjects were genotyped for three biallelic polymorphisms in the promoter region of TNF-angene by direct sequencing of polymerase chain reaction (PCR) products. A polymorphism of thenTNF-b gene (TNFB*n1/TNFB*n2) was detected by Nco I restriction fragment length polymorphismnanalysis of PCR products spanning intron 1 and exon 2 of the TNF-b gene.nResults: None of the polymorphisms conferred susceptibility to sarcoidosis. However, our studynidentified the allele TNFB*n1, detected by the presence of a Nco I restriction site, as a marker ofnprolonged clinical course, with the resolution of sarcoidosis being defined as the disappearancenof all clinical symptoms, physical signs of active lesions, abnormal chest radiograph findings, andnabnormal results of pulmonary function and biochemical tests. When the probability of remissionnin patients homozygous for TNFB*n2 was defined as 1.00, it was 0.48 (95% confidence interval,n0.26 to 0.88; p < 0.05) in patients with TNFB*n1 (genotypes TNFB*n1/1 and TNFB*n1/2).nConclusions: The TNFB*n1 allele is a marker for prolonged clinical course in patients withnsarcoidosis. Our study is the first to link a cytokine gene polymorphism to the prognosis ofnsarcoidosis.