The Clinical Genomic Group, Department of Occupational and Environmental Medicine, National Heart and Lung Institute, Imperial College, London, UK. paolospagnolo@hotmail.com
Sarcoidosis is a heterogeneous disorder with a strong genetic influence. Genetic factors are also thought to influence disease severity and outcome. We sought to determine whether polymorphisms within CCR2 gene predispose to L?fgren's syndrome--a clinically and genetically distinct sarcoidosis phenotype--and, importantly, whether this association is independent of the known association with the HLA-DRB1*0301 allele.
We investigated 5 CCR2 variants and HLA-DRB1*0301 by sequence-specific primer (SSP) polymerase chain reaction (PCR) in 176 Spanish (76 L?fgren's syndrome, 100 controls) and 387 Swedish subjects (126 L?fgren's syndrome, 77 non-L?fgren sarcoidosis, 184 controls).
One of the deduced haplotypes (CCR2 haplotype 2) was associated with L?fgren's syndrome in both Spanish (OR: 2.03, uncorrected P = 0.02; permuted P = 0.041 vs. controls) and Swedish patients (OR: 3.02, uncorrected P = 0.0007; permuted P = 0.0027 vs. non-L?fgren sarcoidosis; OR: 2.46, uncorrected P = 0.0005; permuted P = 0.0031 vs. controls). HLA-DRB1*0301 allele frequency was also increased in Spanish (OR: 3.52, P = 0.0004 vs. controls) and Swedish patients with L?fgren's syndrome (OR: 10.98, P