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C-C Chemokine Receptor 5 Gene Variants in Relation to Lung Disease in Sarcoidosis

2005; American Thoracic Society; Volume: 172; Issue: 6 Linguagem: Inglês

10.1164/rccm.200412-1707oc

1535-4970

Paolo Spagnolo, Elisabetta Renzoni, Athol U. Wells, Susan J. Copley, Sujal R. Desai, Hiroe Sato, Jan C. Grutters, Atiyeh M. Abdallah, Anne B. Taegtmeyer, Roland M. du Bois, Kenneth I. Welsh,

Drug-Induced Adverse Reactions

Genetic factors are likely to influence the clinical course and pattern of sarcoidosis, a granulomatous disease of unknown origin.We tested this hypothesis for C-C chemokine receptor 5 (CCR5), a molecule involved in recruitment and activation of mononuclear cells.In addition to the known CCR5 Delta 32 insertion/deletion, we evaluated a further eight single-nucleotide polymorphisms in 106 British patients and 142 British unaffected subjects, and second-setted the results in 112 Dutch patients and 169 healthy Dutch control subjects.In the British population, the frequency of one of the identified haplotypes (HHC) was strongly associated with the presence of parenchymal disease (radiographic stage >or= II versus stages 0 and I) at presentation (odds ratio [OR], 5.2; 95% confidence interval [CI], 1.96-13.7; corrected p = 0.02), at 2 (OR, 6.6; 95% CI, 2.5-17.6; corrected p = 0.006), and at 4 years follow-up (OR, 6.8; 95% CI, 2.5-18.0; corrected p = 0.0045). In the Dutch population, the same association was seen at 2 (OR, 6.7; 95% CI, 2.8-16.4; corrected p = 0.002), and 4 years follow-up (OR, 9.0; 95% CI, 3.5-23.1; corrected p = 0.0009).No association between the CCR5 haplotype HHC and susceptibility to sarcoidosis was observed, indicating that this relevant gene only operates after disease induction. In summary, we report a strong association between CCR5 haplotype HHC and persistent lung involvement in sarcoidosis.