title: Sarcoidosis susceptibility and resistance HLA-DQB1 alleles in African Americans.
abstract: 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.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Mount Sinai Medical Center, One Gustave Levy Place, Box 1232, NY, NY 10029, USA. michael.iannuzzi@mountsinai.org
authors.forename: Michael C
authors.initials: MC
authors.lastname: Iannuzzi
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Maliarik
authors.forename: Laila M
authors.initials: LM
authors.lastname: Poisson
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Rybicki
mesh_terms: D000483:Alleles; D044383:Black People / Q000235:genetics*; D016022:Case-Control Studies; D018450:Disease Progression; D004781:Environmental Exposure / Q000009:adverse effects / Q000032:analysis; D005787:Gene Frequency / Q000235:genetics; D005799:Genes, Dominant / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006801:Humans; D007113:Immunity, Innate; D015810:Linkage Disequilibrium / Q000235:genetics; D008562:Membrane Glycoproteins; D008824:Michigan; D008957:Models, Genetic; D010375:Pedigree; D010641:Phenotype; D017565:Sarcoidosis, Pulmonary / Q000175:diagnosis / Q000235:genetics*; D012720:Severity of Illness Index; D001741:Black or African American
chemical_list: D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D008562:Membrane Glycoproteins