C-C chemokine receptor 5 gene variants in relation to lung disease in sarcoidosis

Am J Respir Crit Care Med. 2005 Sep 15;172(6):721-8. doi: 10.1164/rccm.200412-1707OC. Epub 2005 Jun 23.


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 >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).

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.

MeSH terms

  • Case-Control Studies
  • England
  • Follow-Up Studies
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genetic Variation*
  • Haplotypes*
  • Humans
  • Netherlands
  • Polymorphism, Single Nucleotide
  • Radiography, Thoracic
  • Receptors, CCR5 / genetics*
  • Sarcoidosis, Pulmonary / diagnostic imaging
  • Sarcoidosis, Pulmonary / ethnology
  • Sarcoidosis, Pulmonary / genetics*
  • Whites / genetics


  • Receptors, CCR5