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; We hypothesized 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 CCR2 were studied in a total of 304 Dutch individuals (90 non-Lofgren sarcoidosis, 47 Lofgren's syndrome, 167 control subjects). From the investigated CCR2 polymorphisms, nine haplo-types were deduced (haplotypes 1-9). In patients with Lofgren's syndrome, a strongly significant increase in the frequency of CCR2haplotype 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-Lofgren sarcoidosis and control subjects (both 38%). The association between CCR2haplotype 2 carriage frequency and Lofgren'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 Lofgren's syndrome. In conclusion, this report describes a strong association between CCR2-haplotype 2 and Lofgren's syndrome. Further studies are needed to understand the molecular mechanisms underlying this association.