BTNL2 allele associations with chronic beryllium disease in HLA-DPB1*Glu69-negative individuals

Tissue Antigens. 2007 Dec;70(6):480-6. doi: 10.1111/j.1399-0039.2007.00944.x. Epub 2007 Oct 8.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Berylliosis / genetics*
  • Butyrophilins
  • Female
  • Genetic Predisposition to Disease*
  • Glutamic Acid* / genetics
  • HLA-DP Antigens / genetics*
  • HLA-DP beta-Chains
  • Homozygote
  • Humans
  • Male
  • Membrane Glycoproteins / genetics*
  • Middle Aged
  • Polymorphism, Genetic
  • White People / genetics


  • BTNL2 protein, human
  • Butyrophilins
  • HLA-DP Antigens
  • HLA-DP beta-Chains
  • HLA-DPB1 antigen
  • Membrane Glycoproteins
  • Glutamic Acid