Association of Human Leukocyte Antigen DRB115 and DRB115:01 Polymorphisms with Response to Immunosuppressive Therapy in Patients with Aplastic Anemia: A Meta-Analysis

• Published in: PloS one 2016-09, Vol.11 (9), p.e0162382-e0162382
• Main Authors: Liu, Shan, Li, Qing, Zhang, Ying, Li, Qiushuang, Ye, Baodong, Wu, Dijiong, Wu, Li, Lu, Hanti, Ji, Conghua
• Format: Article
• Language: English
• Subjects: Alleles; Analysis; Anemia; Anemia, Aplastic - drug therapy; Anemia, Aplastic - genetics; Antigens; Aplastic anemia; Asian Continental Ancestry Group; Autoimmune diseases; Biology and Life Sciences; Bone marrow; Care and treatment; Chinese medicine; Citation analysis; Clinical trials; Cohort analysis; Collaboration; Confidence intervals; Cytotoxicity; Drb1 protein; Gene Frequency; Genetic aspects; Genetic Predisposition to Disease; Genotype; Hematology; Histocompatibility antigen HLA; HLA antigens; HLA-DRB1 Chains - genetics; Hospitals; Humans; Immunosuppressive agents; Immunosuppressive Agents - therapeutic use; Immunotherapy; Leukocytes; Lupus; Lymphocytes; Medical ethics; Medicine and Health Sciences; Meta-analysis; Odds Ratio; Patients; People and Places; Pharmacogenomic Variants; Physical Sciences; Polymorphism, Genetic; Publication Bias; Research and Analysis Methods; Sensitivity analysis; Social sciences; Statistical analysis; Stem cells; Studies; Systematic review; Therapy; Treatment Outcome
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0162382

This study aimed to review and quantitatively analyze (1) the association of aplastic anemia (AA) with human leukocyte antigen (HLA)-DRB1*15 and HLA-DRB1*15:01 polymorphisms and (2) the association of HLA-DRB1*15 and HLA-DRB1*15:01 polymorphisms with response to immunosuppressive therapy (IST) in AA. Published studies have reported conflicting and heterogeneous results regarding the association of HLA-DRB1*15 and HLA-DRB1*15:01 polymorphisms with response to IST in AA. The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese BioMedical Literature, Wangfang and Chinese Social Sciences Citation Index databases were searched. All relevant publications were searched through December 2015. Odds ratio (OR), risk ratio (RR), and 95% confidence intervals (CI) for the comparison between case-control or cohort studies were evaluated. Finally, 24 articles were identified. For HLA-DRB1*15 and HLA-DRB1*15:01, the OR (95% CI) was 2.24(1.33-3.77), P < 0.01 and 2.50(1.73-3.62), P < 0.01, respectively; and the overall pooled RR was 1.72 (1.30-2.29), P < 0.01 and 1.59 (1.29-1.96), P < 0.01, respectively. Statistical evidence showed no publication bias (P > 0.05). Sensitivity analyses revealed that the results were statistically robust. The meta-analysis suggested that HLA-DRB1*15 and HLA-DRB1*15:01 polymorphisms might be associated with increased AA risk in Asians. IST might be more effective in HLA-DRB1*15+ and HLA-DRB1*15:01+ Asian patients with AA than in HLA-DRB1*15- and HLA-DRB1*15:01- Asian patients with AA. Future studies with adequate methodological quality on gene-gene and gene-environment interactions and gene treatment may yield valid results.