C-C chemokine receptor 2 and sarcoidosis: association with Lofgren's syndrome

Sarcoidosis is thought to result from the interaction between an unknown environmental antigenic trigger and the host’s genetic susceptibility.Wehypothesized that sarcoidosis, or one of the disease subsets, could be associated with single nucleotide polymorphisms of C-C chemokine receptor 2 (CCR2) gene. Eight single-nucleotide polymorphisms in CCR2were studied in a total of 304 Dutch individuals (90 non-Lo¨fgren sarcoidosis, 47 Lo¨fgren’s syndrome, 167 control subjects). From the investigated CCR2 polymorphisms, nine haplotypes were deduced (haplotypes 1–9). In patients with Lo¨fgren’s syndrome, a strongly significant increase in the frequency of CCR2-haplotype 2, which includes four unique alleles (A at nucleotide position –6752, A at 3,000, T at 3,547, and T at 4,385), was observed compared with control subjects (74% vs. 38% respectively, p 0.0001), whereas no difference was found between non-Lo¨fgren sarcoidosis and control subjects (both 38%). The association between CCR2-haplotype 2 carriage frequency and Lo¨fgren’s syndrome (odds ratio, 4.4; p 0.0001) remained significant after adjustment for human leukocyte antigen haplotype DRB1*0301-DQB1*0201 (odds ratio, 11.5; p 0.0001) and female sex (odds ratio, 3.2; p 0.003), two known risk factors for Lo¨fgren’s syndrome. In conclusion, this report describes a strong association between CCR2-haplotype 2 and Lo¨fgren’s syndrome. Further studies are needed to understand the molecular mechanisms underlying this association.