Published ahead of print on June 23, 2005, doi:10.1164/rccm.200412-1707OC Am. J. Respir. Crit. Care Med., Volume 172, Number 6, September 2005, 721-728 A more recent version of this article appeared on September 15, 2005
Submitted on December 20, 2004 C-C Chemokine Receptor 5 Gene Variants in Relation to Lung Disease in SarcoidosisPaolo Spagnolo1*,1 Department of Occupational and Environmental Medicine, Imperial College of Science, Technology and Medicine, National Heart and Lung Institute, London, United Kingdom, 2 Department of Radiology, Hammersmith Hospital, London, United Kingdom, 3 Department of Radiology, King's College Hospital, London, United Kingdom, 4 Department of Pulmonology, Sint Antonius Hospital, Nieuwegein, The Netherlands, 5 Heart Science Center, Imperial College, National Heart and Lung Institute, London, United Kingdom * To whom correspondence should be addressed. 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 UK patients and 142 UK unaffected subjects and second setted the results in 112 Dutch patients and 169 healthy Dutch controls. Measurements and Main results: In the UK 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
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II vs. stages 0 and I) at presentation (OR: 5.2; 95% C.I.: 1.96-13.7; corrected p=0.02), at two (OR: 6.6; 95% C.I.:2.5-17.6; corrected p=0.006), and at four years follow up (OR: 6.8; 95% C.I.: 2.5-18.0; corrected p=0.0045). In the Dutch population the same association was seen at two (OR: 6.7; 95% C.I.: 2.8-16.4; corrected p=0.002), and four years follow up (OR: 9.0; 95% C.I.: 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.
