TY - JOUR
T1 - A single nucleotide polymorphism of IL-17 gene in the recipient is associated with acute GVHD after HLA-matched unrelated BMT
AU - Espinoza, J. L.
AU - Takami, A.
AU - Onizuka, M.
AU - Kawase, T.
AU - Sao, H.
AU - Akiyama, H.
AU - Miyamura, K.
AU - Okamoto, S.
AU - Inoue, M.
AU - Ohtake, S.
AU - Fukuda, T.
AU - Morishima, Y.
AU - Kodera, Y.
AU - Nakao, S.
N1 - Funding Information:
We are indebted to Drs Hiroko Oshima, Masanobu Oshima and Atsushi Hirao, Ms Kayoko Yamada, Mayu Yamada and Yuki Motohashi at Kanazawa University, and Dr Keitaro Matsuo at Aichi Cancer Center Research Institute for their technical assistance. We thank all of the Japan Marrow Donor Program transplant teams who have contributed patients and donors to this study. This study was supported by grants from the Ministry of Health, Labor and Welfare, and the Ministry of Education, Culture, sports and Technology, and Funds from the Mitani Research and Development Assistance Organization (Kanazawa, Japan) and by the Japan Leukemia Research Fund (Tokyo, Japan).
PY - 2011/11
Y1 - 2011/11
N2 - IL-17 has an important role in the host defense against extracellular pathogens and the pathophysiology of autoimmune diseases. This study retrospectively examined the impact of a single-nucleotide polymorphism (rs2275913, G197A) in the IL-17 gene of a total 510 recipients with hematologic malignancies and their unrelated donors on the clinical outcomes in HLA-matched myeloablative (discovery study) and nonmyeloablative (validation study) BMT through the Japan Marrow Donor Program (JMDP). In the discovery study, the presence of a 197A genotype in the recipient resulted in a higher incidence of grades II-IV acute GVHD (hazard ratio (HR), 1.87; 95% confidence interval (CI), 1.23-2.85; P=.004). The donor IL-17A genotype did not significantly influence the transplant outcomes. The validation study showed a trend toward an association of the recipient 197A genotype with an increased risk of grades III-IV acute GVHD (HR, 5.84; 95% CI, 0.75-45.72; P=.09), as well as a significantly increased risk for chronic GVHD (HR, 3.86; 95% CI, 1.29-11.59; P=.02). These results suggest an association of the 197A genotype in the recipient side with the development of acute GVHD.
AB - IL-17 has an important role in the host defense against extracellular pathogens and the pathophysiology of autoimmune diseases. This study retrospectively examined the impact of a single-nucleotide polymorphism (rs2275913, G197A) in the IL-17 gene of a total 510 recipients with hematologic malignancies and their unrelated donors on the clinical outcomes in HLA-matched myeloablative (discovery study) and nonmyeloablative (validation study) BMT through the Japan Marrow Donor Program (JMDP). In the discovery study, the presence of a 197A genotype in the recipient resulted in a higher incidence of grades II-IV acute GVHD (hazard ratio (HR), 1.87; 95% confidence interval (CI), 1.23-2.85; P=.004). The donor IL-17A genotype did not significantly influence the transplant outcomes. The validation study showed a trend toward an association of the recipient 197A genotype with an increased risk of grades III-IV acute GVHD (HR, 5.84; 95% CI, 0.75-45.72; P=.09), as well as a significantly increased risk for chronic GVHD (HR, 3.86; 95% CI, 1.29-11.59; P=.02). These results suggest an association of the 197A genotype in the recipient side with the development of acute GVHD.
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U2 - 10.1038/bmt.2010.325
DO - 10.1038/bmt.2010.325
M3 - Article
C2 - 21217785
AN - SCOPUS:80855134362
SN - 0268-3369
VL - 46
SP - 1455
EP - 1463
JO - Bone Marrow Transplantation
JF - Bone Marrow Transplantation
IS - 11
ER -