Vascular endothelial growth factor gene polymorphisms may predict the risk of acute graft-versus-host disease following allogeneic transplantation: preventive effect of vascular endothelial growth factor gene on acute graft-versus-host disease.
Microvessel injury is associated with the development of graft-versus-host disease (GVHD), whereas high levels of posttransplantation vascular endothelial growth factor (VEGF) have a protective effect on severe acute GVHD (aGVHD) and transplantation-related mortality. The current study aimed to determine the impact of VEGFA gene single-nucleotide polymorphisms (SNPs) on the risk of aGVHD after allogeneic stem cell transplantation (SCT). Using polymerase chain reaction and restriction fragment length polymorphism, 4 VEGFA SNPs- -2578 C>A (rs699947), -460 T>C (rs833061), +405 G>C (rs2010963), and +936 C>T (rs3025039)-were analyzed in 98 recipients. Strong linkage disequilibrium was noted among loci -2578, -460, and +405, but not among these loci and locus +936. Accordingly, 4 haplotypes were generated based on the genotypes of -2578, -460, and +405: CTC (47.9%), CTG (26.7%), ACG (24.2%), and CCC (1.0%). The group with low VEGF production (ie, +936CT genotype and 2 copies of the ACG haplotype) had a higher incidence of aGVHD. Significant associations were found between the risk of grade 2-4 aGVHD and the +936 CT (P = .006), -2578 AA (P = .003), and -460 CC (P = .002) genotypes and the ACG haplotype (P = .003). No association between the VEGFA SNPs and chronic GVHD was observed. The VEGFA SNPs might predict a lower risk of aGVHD. Our findings suggest that VEGF may have a protective role in the pathogenesis of aGVHD.
Kim
Dong Hwan
DH
Department of Hematology/Oncology, Kyungpook National University Hospital, Daegu, Korea. drkiim@medimail.co.kr
Lee
Nan Young
NY
Lee
Myung-Hoon
MH
Sohn
Sang Kyun
SK
D000293:Adolescent; D000328:Adult; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D006239:Haplotypes; D006801:Humans; D015994:Incidence; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D012307:Risk Factors; D033581:Stem Cell Transplantation; D014184:Transplantation, Homologous; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A