AUTHOR=Ebbesen Maria , Enevold Christian , Juul Anders , Heilmann Carsten , Sengeløv Henrik , Müller Klaus 

TITLE=Insulin-Like Growth Factor Gene Polymorphisms Predict Clinical Course in Allogeneic Hematopoietic Stem Cell Transplantation

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.01646

DOI=10.3389/fimmu.2020.01646

ISSN=1664-3224

ABSTRACT=<p>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 (<italic>IGF1</italic>), rs978458 (<italic>IGF1</italic>), or rs2854744 (<italic>IGFBP3</italic>) serum levels remained normal during the whole period. In accordance, maximum C-reactive protein levels were lower for these genotypes of <italic>IGF1</italic> (rs1520220: median 66 vs. 102 mg/L, <italic>P</italic> = 0.005 and rs978458: 53 vs. 104 mg/L, <italic>P</italic> &lt; 0.001), translating into borderline significant superior survival (<italic>P</italic> = 0.060 for rs1520220) and reduced treatment-related mortality (<italic>P</italic> = 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.</p>