HLA-DQB1*0201: a marker for good prognosis in British and Dutch patients with sarcoidosis.
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.
D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D048868:Adaptor Proteins, Signal Transducing; D000483:Alleles; D002248:Carbon Monoxide / Q000378:metabolism; D053487:DEAD-box RNA Helicases; D018450:Disease Progression; D004591:Electrophoresis, Polyacrylamide Gel; D005819:Genetic Markers; D006683:HLA-DQ Antigens / Q000235:genetics* / Q000378:metabolism; D059866:HLA-DQ beta-Chains; D006239:Haplotypes; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D008233:Lymphotoxin-alpha / Q000235:genetics; D009426:Netherlands; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011379:Prognosis; D020365:RNA Helicases; D012129:Respiratory Function Tests; D012507:Sarcoidosis / Q000175:diagnosis* / Q000235:genetics*; D013577:Syndrome; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D006113:United Kingdom
D018528:ATP-Binding Cassette Transporters; D048868:Adaptor Proteins, Signal Transducing; D005819:Genetic Markers; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D000949:Histocompatibility Antigens Class II; D008233:Lymphotoxin-alpha; C120111:NFKBIL1 protein, human; D014409:Tumor Necrosis Factor-alpha; D002248:Carbon Monoxide; C498428:DDX39A protein, human; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases