4.5 Article

A single-nucleotide polymorphism of the Fcγ receptor type IIIA gene in the recipient predicts transplant outcomes after HLA fully matched unrelated BMT for myeloid malignancies

Journal

BONE MARROW TRANSPLANTATION
Volume 46, Issue 2, Pages 238-243

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/bmt.2010.88

Keywords

FCGR3A; unrelated donor; single-nucleotide polymorphism

Funding

  1. Ministry of Health, Labor and Welfare
  2. Ministry of Education, Culture, Sports and Technology
  3. Mitani Research and Development Assistance Organization (Kanazawa, Japan)
  4. Japan Leukemia Research Fund (Tokyo, Japan)
  5. Grants-in-Aid for Scientific Research [21591236] Funding Source: KAKEN

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Fc gamma receptor type IIIA (FCGR3A) has a functional single-nucleotide polymorphism (rs396991), at which a G-to T-point mutation results in an amino acid substitution at position 158 (valine to phenylalanine; V158F). This study examined the effect of the FCGR3A polymorphism in donors and recipients on the clinical outcomes in unrelated HLA fully matched myeloablative BMT. The FCGR3A-V158F genotype was retrospectively analyzed in a total of 99 recipients with myeloid malignancies, and their unrelated donors. The presence of the 158V genotype in recipients showed a statistically better OS (adjusted hazard ratio (HR) 0.49; 95% confidence interval (CI) 0.26-0.93; P = 0.03) and TRM (HR 0.30; 95% CI 0.14-0.67; P = 0.003) without significant influence on the relapse rate. The recipient 158V genotype was also associated with a significantly reduced risk of chronic GVHD (HR 0.45; 95% CI 0.20-0.99; P = 0.049) and a trend toward a reduced risk of grade II-IV acute GVHD (HR 0.55; 95% CI 0.27-1.10; P = 0.09), leading to a significantly reduced GVHD-related mortality (HR 0.22; 95% CI 0.06-0.77; P = 0.02). The donor FCGR3A polymorphism did not have any effect on the transplant outcomes. These results suggest an association between the recipient FCGR3A genotype and the clinical outcomes after BMT. Bone Marrow Transplantation (2011) 46, 238-243; doi: 10.1038/bmt.2010.88; published online 19 April 2010

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