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  • Title: A common haplotype of the C-C chemokine receptor 2 gene and HLA-DRB1*0301 are independent genetic risk factors for Löfgren's syndrome.
    Author: Spagnolo P, Sato H, Grunewald J, Brynedal B, Hillert J, Mañá J, Wells AU, Eklund A, Welsh KI, du Bois RM.
    Journal: J Intern Med; 2008 Nov; 264(5):433-41. PubMed ID: 18513341.
    Abstract:
    AIM: 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 Löfgren'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. METHODS: We investigated 5 CCR2 variants and HLA-DRB1*0301 by sequence-specific primer (SSP) polymerase chain reaction (PCR) in 176 Spanish (76 Löfgren's syndrome, 100 controls) and 387 Swedish subjects (126 Löfgren's syndrome, 77 non-Löfgren sarcoidosis, 184 controls). RESULTS: One of the deduced haplotypes (CCR2 haplotype 2) was associated with Löfgren'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-Löfgren 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 Löfgren's syndrome (OR: 10.98, P < 0.0001 vs. non-Löfgren sarcoidosis, OR: 7.71, P < 0.0001 vs. controls). Finally, multivariate analysis revealed that the CCR2 association was independent of HLA-DRB1*0301 in both Spanish (P = 0.02 vs. controls) and Swedish cohorts (P = 0.002 vs. non-Löfgren sarcoidosis, P = 0.001 vs. controls). CONCLUSIONS: This study confirms that CCR2 haplotype 2 and HLA-DRB1*0301 are independent genetic risk factors for Löfgren's syndrome.
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