Published ahead of print on June 23, 2005, doi:10.1164/rccm.200412-1707OC
© 2005 American Thoracic Society doi: 10.1164/rccm.200412-1707OC C-C Chemokine Receptor 5 Gene Variants in Relation to Lung Disease in SarcoidosisClinical Genomic Group, National Heart and Lung Institute, Department of Occupational and Environmental Medicine, Imperial College of Science, Technology and Medicine; Department of Radiology, Hammersmith Hospital; Department of Radiology, King's College Hospital; Heart Science Center, Harefield, National Heart and Lung Institute, Imperial College, London, United Kingdom; and Department of Pulmonology, Sint Antonius Hospital, Nieuwegein, The Netherlands Correspondence and requests for reprints should be addressed to Paolo Spagnolo, Clinical Genomics Group, Imperial College, 1B Manresa Road, London SW3 6LR, UK. E-mail: p.spagnolo{at}imperial.ac.uk
Rationale: Genetic factors are likely to influence the clinical course and pattern of sarcoidosis, a granulomatous disease of unknown origin. Objectives: We tested this hypothesis for C-C chemokine receptor 5 (CCR5), a molecule involved in recruitment and activation of mononuclear cells. Methods: 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. Measurements and Main results: In the British population, the frequency of one of the identified haplotypes (HHC) was strongly associated with the presence of parenchymal disease (radiographic stage
Key Words: cytokines • genetic polymorphisms • sarcoidosis This article has been cited by other articles:
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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). Conclusions: 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. 
