Insulin-Like Growth Factor Gene Polymorphisms Predict Clinical Course in Allogeneic Hematopoietic Stem Cell Transplantation
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Insulin-Like Growth Factor Gene Polymorphisms Predict Clinical Course in Allogeneic Hematopoietic Stem Cell Transplantation. / Ebbesen, Maria; Enevold, Christian; Juul, Anders; Heilmann, Carsten; Sengeløv, Henrik; Müller, Klaus.
I: Frontiers in Immunology, Bind 11, 1646, 2020.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Insulin-Like Growth Factor Gene Polymorphisms Predict Clinical Course in Allogeneic Hematopoietic Stem Cell Transplantation
AU - Ebbesen, Maria
AU - Enevold, Christian
AU - Juul, Anders
AU - Heilmann, Carsten
AU - Sengeløv, Henrik
AU - Müller, Klaus
PY - 2020
Y1 - 2020
N2 - Allogeneic hematopoietic stem cell transplantation (HSCT) is challenged by significant toxicities that are propagated by systemic inflammation caused by cytotoxic damage. Insulin-like growth factor-1 (IGF-1) is key in repair of most tissues and is to a large extent genetically determined. We investigated eight single nucleotide polymorphisms (SNPs) in the genes encoding IGF-1 and its binding protein (IGFBP3) in 543 patients undergoing HSCT to access their impact on systemic inflammation and clinical outcomes. Overall, median serum levels of both IGF-1 and IGFBP3 were found reduced from the referral until 2 years post-HSCT compared with healthy sex- and age-matched individuals, but, for individuals homozygous of the known high-producer minor allele of rs1520220 (IGF1), rs978458 (IGF1), or rs2854744 (IGFBP3) serum levels remained normal during the whole period. In accordance, maximum C-reactive protein levels were lower for these genotypes of IGF1 (rs1520220: median 66 vs. 102 mg/L, P = 0.005 and rs978458: 53 vs. 104 mg/L, P < 0.001), translating into borderline significant superior survival (P = 0.060 for rs1520220) and reduced treatment-related mortality (P = 0.050 for rs978458). In conclusion, we found that three SNPs in the IGF-1 axis with known functional impact were associated with circulating IGF-1 or IGFBP-3 levels also in the setting of HSCT, and predictive of the severity of the toxic-inflammatory response during the treatment.
AB - Allogeneic hematopoietic stem cell transplantation (HSCT) is challenged by significant toxicities that are propagated by systemic inflammation caused by cytotoxic damage. Insulin-like growth factor-1 (IGF-1) is key in repair of most tissues and is to a large extent genetically determined. We investigated eight single nucleotide polymorphisms (SNPs) in the genes encoding IGF-1 and its binding protein (IGFBP3) in 543 patients undergoing HSCT to access their impact on systemic inflammation and clinical outcomes. Overall, median serum levels of both IGF-1 and IGFBP3 were found reduced from the referral until 2 years post-HSCT compared with healthy sex- and age-matched individuals, but, for individuals homozygous of the known high-producer minor allele of rs1520220 (IGF1), rs978458 (IGF1), or rs2854744 (IGFBP3) serum levels remained normal during the whole period. In accordance, maximum C-reactive protein levels were lower for these genotypes of IGF1 (rs1520220: median 66 vs. 102 mg/L, P = 0.005 and rs978458: 53 vs. 104 mg/L, P < 0.001), translating into borderline significant superior survival (P = 0.060 for rs1520220) and reduced treatment-related mortality (P = 0.050 for rs978458). In conclusion, we found that three SNPs in the IGF-1 axis with known functional impact were associated with circulating IGF-1 or IGFBP-3 levels also in the setting of HSCT, and predictive of the severity of the toxic-inflammatory response during the treatment.
KW - hematopoietic stem cell transplantation
KW - insulin-like growth factor-1
KW - single nucleotide polymorphisms
KW - systemic inflammation
KW - toxicity
U2 - 10.3389/fimmu.2020.01646
DO - 10.3389/fimmu.2020.01646
M3 - Journal article
C2 - 32793242
AN - SCOPUS:85089347686
VL - 11
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
M1 - 1646
ER -
ID: 254461177