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

A. Takami, J. L. Espinoza, M. Onizuka, K. Ishiyama, T. Kawase, Y. Kanda, H. Sao, H. Akiyama, K. Miyamura, Shinichiro Okamoto, M. Inoue, S. Ohtake, T. Fukuda, Y. Morishima, Y. Kodera, S. Nakao

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Abstract

Fcγ 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.

Original languageEnglish
Pages (from-to)238-243
Number of pages6
JournalBone Marrow Transplantation
Volume46
Issue number2
DOIs
Publication statusPublished - 2011 Feb

Fingerprint

Fc Receptors
Single Nucleotide Polymorphism
Confidence Intervals
Genotype
Genes
Neoplasms
Tissue Donors
Unrelated Donors
Valine
Amino Acid Substitution
Phenylalanine
Point Mutation
Transplant Recipients
Transplants
Recurrence
Mortality

Keywords

  • FCGR3A
  • single-nucleotide polymorphism
  • unrelated donor

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

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. / Takami, A.; Espinoza, J. L.; Onizuka, M.; Ishiyama, K.; Kawase, T.; Kanda, Y.; Sao, H.; Akiyama, H.; Miyamura, K.; Okamoto, Shinichiro; Inoue, M.; Ohtake, S.; Fukuda, T.; Morishima, Y.; Kodera, Y.; Nakao, S.

In: Bone Marrow Transplantation, Vol. 46, No. 2, 02.2011, p. 238-243.

Research output: Contribution to journalArticle

Takami, A, Espinoza, JL, Onizuka, M, Ishiyama, K, Kawase, T, Kanda, Y, Sao, H, Akiyama, H, Miyamura, K, Okamoto, S, Inoue, M, Ohtake, S, Fukuda, T, Morishima, Y, Kodera, Y & Nakao, S 2011, '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', Bone Marrow Transplantation, vol. 46, no. 2, pp. 238-243. https://doi.org/10.1038/bmt.2010.88
Takami, A. ; Espinoza, J. L. ; Onizuka, M. ; Ishiyama, K. ; Kawase, T. ; Kanda, Y. ; Sao, H. ; Akiyama, H. ; Miyamura, K. ; Okamoto, Shinichiro ; Inoue, M. ; Ohtake, S. ; Fukuda, T. ; Morishima, Y. ; Kodera, Y. ; Nakao, S. / 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. In: Bone Marrow Transplantation. 2011 ; Vol. 46, No. 2. pp. 238-243.
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abstract = "Fcγ 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.",
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AU - Takami, A.

AU - Espinoza, J. L.

AU - Onizuka, M.

AU - Ishiyama, K.

AU - Kawase, T.

AU - Kanda, Y.

AU - Sao, H.

AU - Akiyama, H.

AU - Miyamura, K.

AU - Okamoto, Shinichiro

AU - Inoue, M.

AU - Ohtake, S.

AU - Fukuda, T.

AU - Morishima, Y.

AU - Kodera, Y.

AU - Nakao, S.

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N2 - Fcγ 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.

AB - Fcγ 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.

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