title: BTNL2 allele associations with chronic beryllium disease in HLA-DPB1*Glu69-negative individuals.
abstract: Butyrophilin-like 2 (BTNL2) polymorphisms have been associated with sarcoidosis. We hypothesized that BTNL2 variants might confer a human leukocyte antigen (HLA)-independent risk for chronic beryllium disease (CBD), a granulomatous lung disease with similar clinical, radiological, and pathological features to sarcoidosis. Genomic DNA was obtained from CBD (n= 88), beryllium sensitized (BeS, n= 86), and beryllium exposed nondiseased control subjects (Be-exp, n= 173). Six BTNL2 polymorphisms, HLA-DPB1, DRB1, and DQB1 alleles were determined by sequence-specific primer-PCR. All BTNL2 polymorphisms were in Hardy-Weinberg equilibrium. No significant differences were found between BTNL2 polymorphisms or haplotypes and CBD, BeS, or Be-exp. In HLA-DPB1*Glu69-negative subjects (n= 10 CBD, n= 13 BeS, n= 102 Be-exp), DRB1*13 and BTNL2 rs3117099TT homozygosity were increased in CBD (70% and 40%, respectively) vs Be-exp (16%, P= 0.001 and 2.9%, P= 0.001, respectively). The BTNL2 rs3117099T-HLA-DRB1*13 combination was significantly increased in CBD (50%) compared with Be-exp (6.9%, P= 0.001). In conclusion, both DRB1*13 and rs3117099TT homozygosity are associated with CBD in *Glu69-negative subjects, while DPB1*Glu69 is associated with CBD and BeS compared with Be-exp. As a result of the small sample size and strong linkage disequilibrium between DRB1*13-DQB1*0603/4/9 and the BTNL2 rs3117099T allele, it is difficult to assess the primary association in DPB1*Glu69-negative CBD cases.
authors.affiliation: Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206, USA.
authors.forename: H
authors.initials: H
authors.lastname: Sato
authors.forename: P
authors.initials: P
authors.lastname: Spagnolo
authors.forename: L
authors.initials: L
authors.lastname: Silveira
authors.forename: K I
authors.initials: KI
authors.lastname: Welsh
authors.forename: R M
authors.initials: RM
authors.lastname: du Bois
authors.forename: L S
authors.initials: LS
authors.lastname: Newman
authors.forename: L A
authors.initials: LA
authors.lastname: Maier
mesh_terms: D000483:Alleles; D001607:Berylliosis / Q000235:genetics*; D000071797:Butyrophilins; D005260:Female; D020022:Genetic Predisposition to Disease; D018698:Glutamic Acid / Q000235:genetics; D006682:HLA-DP Antigens / Q000235:genetics*; D059868:HLA-DP beta-Chains; D006720:Homozygote; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D044465:White People / Q000235:genetics
chemical_list: C408263:BTNL2 protein, human; D000071797:Butyrophilins; D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; D008562:Membrane Glycoproteins; D018698:Glutamic Acid