IL-6 and IL-10 promoter gene polymorphisms of patients and donors of allogeneic sibling hematopoietic stem cell transplants associate with the risk of acute graft-versus-host disease.
The present study aimed to determine existing associations between single nucleotide polymorphisms within the promoters of interleukin (IL)-6 (-174 G/C) and IL-10 (-1082 G/A, -819 C/T, -592 C/A) genes and the outcome of allogeneic sibling hematopoietic stem cell transplantation. Ninety-three recipients and 74 donors were typed for IL-6 and IL-10 alleles by polymerase chain reaction-sequence specific primer. Then, IL-6 activity in patient serum and the concentration of C-reactive protein were analyzed at various times after transplantation in relation to transplant complications and IL-6 genotype. IL-6 activity in serum was significantly higher in patients who died as a result of toxic complications and after the 6 weeks after transplantation in patients with severe acute graft-versus-host disease (aGVHD). Recipient IL-6 G genotype was associated with increased IL-6 activity and C-reactive protein production. In univariate analyses, recipient IL-6 G and donor IL-6 GG associated or tended to associate with increased risk for aGVHD. In contrast, recipient IL-10 GCC/GCC and donor IL-10 ACC decreased the risk of aGVHD. IL-6 and IL-10 polymorphic features, together with other factors known to affect the risk of aGVHD, were also subjected to multivariate analyses. These analyses confirmed the independent contribution of recipient IL-10 GCC/GCC (odds ratio = 0.085, p = 0.046) and donor IL-6 GG (odds ratio = 3.934, p = 0.034) genotypes to the risk of aGVHD.
Lower Silesian Center for Cellular Transplantation and National Polish Bone Marrow Donor Registry, Wroclaw, Poland. lkarabon@wp.pl
Lidia
L
Karabon
Barbara
B
Wysoczanska
Katarzyna
K
Bogunia-Kubik
Krzysztof
K
Suchnicki
Andrzej
A
Lange
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006086:Graft vs Host Disease / Q000150:complications / Q000235:genetics* / Q000401:mortality; D018380:Hematopoietic Stem Cell Transplantation / Q000706:statistics & numerical data; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D014019:Tissue Donors
D015850:Interleukin-6; D016753:Interleukin-10; D002097:C-Reactive Protein