Sarcoidosis Susceptibility and Resistance HLA-DQB1 Alleles in African Americans

• Published in: American journal of respiratory and critical care medicine 2003-05, Vol.167 (9), p.1225-1231
• Main Authors: Iannuzzi, Michael C, Maliarik, Mary J, Poisson, Laila M, Rybicki, Benjamin A
• Format: Article
• Language: English
• Subjects: African Americans; Alleles; Antigens; Biological and medical sciences; Black or African American; Black People - genetics; Case-Control Studies; Chronic illnesses; Disease Progression; Environmental Exposure - adverse effects; Environmental Exposure - analysis; Gene Frequency - genetics; Genes, Dominant - genetics; Genetic Predisposition to Disease - genetics; Genetic Variation - genetics; Genotype; Granulomas; HLA-DQ Antigens - genetics; HLA-DQ beta-Chains; Humans; Immunity, Innate; Linkage Disequilibrium - genetics; Medical sciences; Membrane Glycoproteins; Michigan; Models, Genetic; Nuclear family; Pedigree; Phenotype; Questionnaires; Sarcoidosis; Sarcoidosis, Pulmonary - diagnosis; Sarcoidosis, Pulmonary - genetics; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Severity of Illness Index
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200209-1097OC

Sarcoidosis, in the United States, more commonly and severely affects African Americans. HLA associations with sarcoidosis have been reported, but most studies used case-control designs, which may produce biased results because of population stratification. We examined transmission of HLA-DQB1 alleles in 225 African American families with at least one offspring with sarcoidosis. Of five low-resolution HLA-DQB1 alleles, *02 and *06 showed significant deviation in transmission patterns to affected offspring. High-resolution typing of these allelic subsets revealed that HLA-DQB1*0201 was transmitted to affected offspring half as often as expected (p = 0.001), whereas DQB1*0602 was transmitted to affected offspring about 20% more often than expected (p = 0.029). Examining interactions between *0201 and *0602 alleles and environmental exposures showed that *0602 varied little with respect to exposure, but sarcoidosis risk associated with *0201 often depended on exposure status. Alternatively, the *0602 allele in affected probands was associated with radiographic disease progression, but the *0201 allele showed no significant correlation with phenotype. Major differences in the amino acid sequences encoded by *0201 and *0602 alleles exist, which may explain the differential effects these alleles have on sarcoidosis susceptibility and progression in African Americans.