Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Severe aplastic anemia (SAA) is a heterogeneous hematological disorder with a high mortality. Genetic predisposition has been shown to play a role in a considerable proportion of SAA cases. For instance, the human lymphocyte antigen HLA-DR2 has been repeatedly demonstrated to be over-represented in SAA patients. In this paper, we expand on the evidence for the contribution of HLA polymorphism in the susceptibility to SAA, which was obtained using the "high-resolution" technique of HLA-DRB1 subtyping. The DRB1*1501 allele appeared to be responsible for the predominance of DR2 specificity in SAA patients and was the most significant risk factor for this disease. It was observed in 23/44 (52.3%) patients versus 22/100 (22.0%) donors [odds ratio (OR) = 3.9; 95% confidence interval (CI): 1.8-8.3; P = 0.0005, corrected P (Pc) < 0.05]. In addition, DRB1*04 alleles also displayed non-random distribution in the SAA group. In particular, DRB1*04 variants coding for alanine at position 74 of the DR beta 1 chain (HLA-DR4-Ala74 beta subtype) were detected in all 13 DR4-positive SAA patients but only in 15/24 (62.5%) controls (OR = 16.6; 95% CI: 0.9-312.0; P = 0.015). Multiple comparison analysis confirmed that the HLA-DR4-Ala74 beta subtype confers susceptibility to SAA independently from the DRB1*1501 allele. Finally, examination of the clinical records has shown that the HLA-DR4-Ala74 beta subtype is associated with poor outcome of SAA.
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PMID:HLA-DR4-Ala74 beta is associated with risk and poor outcome of severe aplastic anemia. 1126 26

HLA-DR15 (DR2) is overrepresented in aplastic anemia (AA) patients, and its presence is associated with a better response to cyclosporine-based immunosuppressive therapy (IST). However, little is known about other human leukocyte antigen (HLA) alleles affecting therapy response. We investigated 37 Korean patients with severe AA for the association of HLA class II alleles with response to IST: cyclosporine A combined with antithymocyte globulin or antilymphocyte globulin. Molecular or serologic typing of HLA-DR and HLA-DQ alleles was performed. In responders (13/37, 35.1%), the frequency of HLA-DR15 was increased (69.2% vs 8.3%, p = 0.0002) and that of DR4 was decreased (7.7% vs 66.7%, p = 0.0007) compared with nonresponders. The response rate was significantly higher in DR15(+) than in DR15(-) (81.8% vs 15.4%, p = 0.0002) and in DR4(-) than in DR4(+) patients (60.0% vs 5.9%, p = 0.0007). The response rates in the best (DR15(+)/DR4(-)), intermediate, and poor response groups (DR15(-)/DR4(+)) were 88.9, 38.5, and 0%, respectively (p = 0.00001). At the allelic level, DRB1*1501 and closely linked DQB1*0602 were associated with a good response and DRB1*0405 and closely linked DQB1*0401 with a poor response to IST. HLA-DR typing may be useful for predicting a response to IST in AA patients.
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PMID:Association of human leukocyte antigen class II alleles with response to immunosuppressive therapy in Korean aplastic anemia patients. 1981 81