Cytokine gene polymorphisms and their associations with graft-versus-host disease (GVHD).
| Cytokine Gene Polymorphism . | Proposed Function of Polymorphism . | Effect of Recipient (R) or Donor (D) Genotype on Hematopoietic Stem Cell Transplantation Outcome . |
|---|---|---|
| Abbreviations: TNF, tumor necrosis factor; HLA, human leukocyte antigen; BMT, bone marrow transplant; IL, interleukin; IFN, interferon; TGF, transforming growth factor. | ||
| TNFd3 | ||
| Middleton et al 19984 | Pro-inflammatory | R genotype |
| Cavet et al 199919 | Upregulates TNFα production | Increases aGVHD in HLA-matched sibling BMT4,19 |
| Kögler et al 200270 | No association cord blood transplantation70 | |
| TNF receptor | Unknown | D genotype. |
| TNFRII 196R | (TNFRII receptor stimulates T cell proliferation and alloimmune responses) | More severe GVHD in MUD transplants20 |
| Ishikawa et al 200220 | D genotype | |
| Stark et al 200322 | Incidence of acute and chronic GVHD | |
| HLA-matched siblings22 | ||
| IL-10−1064(12–15) | ||
| Middleton et al 19984 | Anti-inflammatory | R genotype |
| Cavet et al 199919 | Haplotype associated with decreased production of IL-10 | Increase in GVHD in HLA-matched sibling BMT4,19 |
| Socié et al 200126 | R & D genotype associated with acute GVHD26 | |
| Kögler et al 200269 | No association in cord blood transplantation69 | |
| IL-6−174 | ||
| Cavet et al 199919 | Pro-inflammatory | Increases acute and chronic GVHD in |
| Socié et al 200126 | G allele associated with increased IL-6 production | HLA-matched sibling cohorts.19 |
| D genotype | ||
| IFNγ Intron 1 allele 3 | Pro-inflammatory | R genotype |
| Cavet et al 200125 | Lower in vitro IFNγ production | Increased acute GVHD in HLA-matched sibling cohorts25 |
| IL-1 gene family | Pro-inflammatory | D genotype associates with chronic |
| IL-1α889;intron 6 VNTR | GVHD in HLA-matched siblings70 | |
| Cullup et al 200229 | Improved survival decreases TRM; | |
| MacMillan et al 200330 | D or R genotype in MUD transplants30 | |
| IL-1 Ra VNTR | Anti-inflammatory | D genotype |
| VNTR intron 2 | Downregulates pro-inflammatory effects of IL-1 | Increases chronic GVHD29 and increases in acute GVHD in HLA-matched siblings18,28 |
| Cullup et al 2001,200328,29 | ||
| Rocha et al 200218 | ||
| TGFβTGF-509 | C allele at -509 associated with increased TGFβ production | No association with TGFβ −509 with incidence of GVHD or outcome in HLA-matched sibling cohort.25,31 Also association with GVHD incidence and high TGFβ producers in pediatric HLA-matched sibling cohort. R genotype71 |
| Cavet et al 200125 | ||
| Grainger et al 199931 | ||
| Tambur et al 200171 | ||
| Hattori et al 200232 | ||
| TGF-β1 codon 10 leucine/proline | Development of acute GVHD in MUD pediatric transplants32 | |
| Cytokine Gene Polymorphism . | Proposed Function of Polymorphism . | Effect of Recipient (R) or Donor (D) Genotype on Hematopoietic Stem Cell Transplantation Outcome . |
|---|---|---|
| Abbreviations: TNF, tumor necrosis factor; HLA, human leukocyte antigen; BMT, bone marrow transplant; IL, interleukin; IFN, interferon; TGF, transforming growth factor. | ||
| TNFd3 | ||
| Middleton et al 19984 | Pro-inflammatory | R genotype |
| Cavet et al 199919 | Upregulates TNFα production | Increases aGVHD in HLA-matched sibling BMT4,19 |
| Kögler et al 200270 | No association cord blood transplantation70 | |
| TNF receptor | Unknown | D genotype. |
| TNFRII 196R | (TNFRII receptor stimulates T cell proliferation and alloimmune responses) | More severe GVHD in MUD transplants20 |
| Ishikawa et al 200220 | D genotype | |
| Stark et al 200322 | Incidence of acute and chronic GVHD | |
| HLA-matched siblings22 | ||
| IL-10−1064(12–15) | ||
| Middleton et al 19984 | Anti-inflammatory | R genotype |
| Cavet et al 199919 | Haplotype associated with decreased production of IL-10 | Increase in GVHD in HLA-matched sibling BMT4,19 |
| Socié et al 200126 | R & D genotype associated with acute GVHD26 | |
| Kögler et al 200269 | No association in cord blood transplantation69 | |
| IL-6−174 | ||
| Cavet et al 199919 | Pro-inflammatory | Increases acute and chronic GVHD in |
| Socié et al 200126 | G allele associated with increased IL-6 production | HLA-matched sibling cohorts.19 |
| D genotype | ||
| IFNγ Intron 1 allele 3 | Pro-inflammatory | R genotype |
| Cavet et al 200125 | Lower in vitro IFNγ production | Increased acute GVHD in HLA-matched sibling cohorts25 |
| IL-1 gene family | Pro-inflammatory | D genotype associates with chronic |
| IL-1α889;intron 6 VNTR | GVHD in HLA-matched siblings70 | |
| Cullup et al 200229 | Improved survival decreases TRM; | |
| MacMillan et al 200330 | D or R genotype in MUD transplants30 | |
| IL-1 Ra VNTR | Anti-inflammatory | D genotype |
| VNTR intron 2 | Downregulates pro-inflammatory effects of IL-1 | Increases chronic GVHD29 and increases in acute GVHD in HLA-matched siblings18,28 |
| Cullup et al 2001,200328,29 | ||
| Rocha et al 200218 | ||
| TGFβTGF-509 | C allele at -509 associated with increased TGFβ production | No association with TGFβ −509 with incidence of GVHD or outcome in HLA-matched sibling cohort.25,31 Also association with GVHD incidence and high TGFβ producers in pediatric HLA-matched sibling cohort. R genotype71 |
| Cavet et al 200125 | ||
| Grainger et al 199931 | ||
| Tambur et al 200171 | ||
| Hattori et al 200232 | ||
| TGF-β1 codon 10 leucine/proline | Development of acute GVHD in MUD pediatric transplants32 | |