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 singlenucleotide 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 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.

A common haplotype of the CC chemokine receptor 5 is associated with lung involvement in sarcoidosis / Spagnolo, Paolo; Renzoni, Ea; Wells, Au; Copley, Sj; Desai, Sr; Sato, H; Grutters, Jc; Abdallah, A; Taegtmeyer, A; du Bois, Rm; Welsh, Ki. - In: AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE. - ISSN 1073-449X. - STAMPA. - 172(2005), pp. 721-728.

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