title: FcγRIIa-H131R variant is associated with inferior response in diffuse large B cell lymphoma: A meta-analysis of genetic risk.
abstract: OBJECTIVE
  Low-affinity variants FcγRIIIa-V158F and FcγRIIa- H131R may alter response to rituximab-based chemotherapy in diffuse large B-cell lymphoma (DLBCL) but available clinical evidence is inconclusive. Our purpose was to explore their association in terms of treatment response.
  
  
  METHODS
  We performed a meta-analysis of published literature to associate these variants with complete remission after upfront immunochemotherapy in DLBCL, and summarized the genetic risk using the model-free approach of generalized odds ratio (ORG). PubMed and EMBASE search (up to July 2014) yielded five pertinent studies.
  
  
  RESULTS
  FcγRIIa-H131R was associated with an inferior response to treatment (ORG0.67; 95%CI 0.46-0.97) and an additive mode of inheritance, with the genetic risk of heterozygotes assigned in the middle between high affinity (H/H) and lower affinity (R/R) genotypes. This effect was unrelated to risk stratification, as no association was documented for FcγRIIa-H131R variant with the international prognostic index (IPI) (ORG1.02; 95%CI 0.79-1.31 for IPI 3-5 over 0-2). FcγRIIIa-V158F had no impact on treatment response but linkage disequilibrium and defective antibody-dependent cell-mediated cytotoxicity may have affected the outcome.
  
  
  CONCLUSIONS
  FcγRIIa-H131R but not FcγRIIIa-V158F may modify treatment response in DLBCL.
authors.affiliation: Warren Alpert Medical School of Brown University, Providence RI, USA.
authors.forename: Panayiotis D
authors.initials: PD
authors.lastname: Ziakas
authors.forename: Loukia S
authors.initials: LS
authors.lastname: Poulou
authors.forename: Elias
authors.initials: E
authors.lastname: Zintzaras
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005787:Gene Frequency; D056726:Genetic Association Studies; D040941:Heredity; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D015810:Linkage Disequilibrium; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D016017:Odds Ratio; D010597:Pharmacogenetics; D000071184:Pharmacogenomic Variants; D010641:Phenotype; D017452:Receptors, IgG / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D000069283:Rituximab / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C445323:FCGR2A protein, human; D017452:Receptors, IgG; D000069283:Rituximab