Spagnolo Paolo, Renzoni Elisabetta A, Wells Athol U, Copley Susan J, Desai Sujal R, Sato Hiroe, Grutters Jan C, Abdallah Atiyeh, Taegtmeyer Anne, du Bois Roland M, Welsh Kenneth I
Clinical Genomic Group, National Heart and Lung Institute, Department of Occupational and Environmental Medicine, Imperial College of Science, Technology and Medicine, London, UK.
Am J Respir Crit Care Med. 2005 Sep 15;172(6):721-8. doi: 10.1164/rccm.200412-1707OC. Epub 2005 Jun 23.
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.
