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Sarcoidosis Susceptibility and Resistance HLA-DQB1 Alleles in African Americans

Division of Pulmonary and Critical Care Medicine, Mount Sinai Medical Center, New York, New York; and Department of Pulmonary, Critical Care, Allergy, and Sleep Medicine and Department of Biostatistics and Research Epidemiology, Henry Ford Health System, Detroit, Michigan

Correspondence and requests for reprints should be addressed to Michael C. Iannuzzi, M.D., Division of Pulmonary and Critical Care Medicine, Mount Sinai Medical Center, One Gustave Levy Place, Box 1232, NY, NY 10029. E-mail: michael.iannuzzi{at}mountsinai.org

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.

Key Words: African Americans • disease susceptibility • genetic predisposition • HLA antigens • sarcoidosis

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