HLA-DQB1*0201: a marker for good prognosis in British and Dutch patients with sarcoidosis

Am J Respir Cell Mol Biol. 2002 Oct;27(4):406-12. doi: 10.1165/rcmb.4782.


Human leukocyte antigen (HLA)-DQB1 is one of the intriguing candidate genes in sarcoidosis. We performed high resolution molecular HLA-DQB1 typing on two groups of white patients (British [UK] and Dutch [NL]) in order to investigate the relationship between 19 DQB1 alleles and disease severity and progression. A total of 803 individuals were studied (133 UK and 102 NL patients, and 354 UK and 214 NL control subjects). Disease severity data included extrapulmonary disease, chest X-ray stage, lung diffusing capacity for carbon monoxide, and FVC. Progression was evaluated on follow-up chest radiographs (2 and 4 yr). The results showed DQB1*0201 to be strongly protective against severe sarcoidosis in both populations; in other words, it localized to Stage I at all time points (P < 0.0001, P(corrected) (P(c)) = 0.002), whereas another DQB1 allele, *0602, tended to have opposite effects. Further, a clear association was found between the *0201 allele and Löfgren's syndrome (P < 0.0001, P(c) = 0.001). More importantly, carriage of this allele reduced the risk of disease progression. In contrast, the other common split of DQB1*02, *0202, did not affect disease severity but was mildly protective against sarcoidosis in the UK population (P = 0.02, p(c) not significant). In conclusion, this study shows that DQB1*0201 is a strong marker for mild sarcoidosis. Additional mapping across the DQB1*0201-DRB1*0301 haplotype, including specific alleles at genes such as DRB3, tumor necrosis factor, lymphotoxin-alpha, I-kappa-B-like protein, and B-associated transcript 1, is necessary for a final localization of the protective effect on this haplotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • Adaptor Proteins, Signal Transducing
  • Alleles
  • Carbon Monoxide / metabolism
  • DEAD-box RNA Helicases
  • Disease Progression
  • Electrophoresis, Polyacrylamide Gel
  • Genetic Markers*
  • HLA-DQ Antigens / genetics*
  • HLA-DQ Antigens / metabolism
  • HLA-DQ beta-Chains
  • Haplotypes
  • Histocompatibility Antigens Class II / genetics
  • Humans
  • Lymphotoxin-alpha / genetics
  • Netherlands
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Prognosis
  • RNA Helicases
  • Respiratory Function Tests
  • Sarcoidosis / diagnosis*
  • Sarcoidosis / genetics*
  • Syndrome
  • Time Factors
  • Tumor Necrosis Factor-alpha / genetics
  • United Kingdom


  • ATP-Binding Cassette Transporters
  • Adaptor Proteins, Signal Transducing
  • Genetic Markers
  • HLA-DQ Antigens
  • HLA-DQ beta-Chains
  • HLA-DQB1 antigen
  • Histocompatibility Antigens Class II
  • Lymphotoxin-alpha
  • NFKBIL1 protein, human
  • Tumor Necrosis Factor-alpha
  • Carbon Monoxide
  • DDX39A protein, human
  • DEAD-box RNA Helicases
  • RNA Helicases