Abstract
An increasing number of gene polymorphisms of immune regulatory molecules are being associated with clinical performance following stem cell transplantation (SCT). These polymorphisms affect structural or regulatory changes on immune regulatory molecules including cytokines (1–11), steroid hormone family receptors (12,13), pathogen effectors such as mannose binding lectins (14), and response mediators such as the Fas signaling system (15).
In contrast to polymorphisms of the major histocompatibility complex, the genome variations found in these non-human leukocyte antigen genes are simple to detect, allowing studies to be done in many laboratories and transplant centres. Many forms of DNA polymorphism detection are now available, allowing even modest laboratories to mount studies of their own. Despite these advances, studies in SCT have a number of problems relating to the complex clinical situation that they study; issues of study design and data interpretation in transplant studies are complex and challenging and are the main limiting factors, which inhibit progress in confirming genetic features which influence the success of SCT.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Cavet, J., Dickinson, A. M., Norden, J., Taylor, P. R., Jackson, G. H., and Middleton, P. G. (2001) Interferon-gamma and interleukin-6 gene polymorphisms associate with graft-versus-host disease in HLA-matched sibling bone marrow transplantation. Blood 98, 1594–1600.
Cavet, J., Middleton, P. G., Segall, M., Noreen, H., Davies, S. M., and Dickinson, A. M. (1999) Recipient tumor necrosis factor-alpha and interleukin-10 gene polymorphisms associate with early mortality and acute graft-versus-host disease severity in HLA-matched sibling bone marrow transplants. Blood 94, 3941–3946.
Cullup, H., Dickinson, A. M., Cavet, J., Jackson, G. H., and Middleton, P. G. (2003) Polymorphisms of interleukin-1 alpha constitute independent risk factors for chronic graft-versus-host disease after allogeneic bone marrow transplantation. Br. J. Haematol. 122, 778–787.
Cullup, H., Dickinson, A. M., Jackson, G. H., Taylor, P. R., Cavet, J., and Middleton, P. G. (2001) Donor interleukin 1 receptor antagonist genotype associated with acute graft-versus-host disease in human leucocyte antigen-matched sibling allogeneic transplants. Br. J. Haematol. 113, 807–813.
Ishikawa, Y., Kashiwase, K., Akaza, T., et al. (2002) Polymorphisms in TNFA and TNFR2 affect outcome of unrelated bone marrow transplantation. Bone Marrow Transplant 29, 569–575.
Keen, L. J., DeFor, T. E., Bidwell, J. L., Davies, S. M., Bradley, B. A., and Hows, J. M. (2004) Interleukin-10 and tumor necrosis factor alpha region haplotypes predict transplant mortality after unrelated donor stem cell transplantation. Blood 103, 3599–3602.
MacMillan, M. L., Radloff, G. A., DeFor, T. E., Weisdorf, D. J., and Davies, S. M. (2003) Interleukin-1 genotype and outcome of unrelated donor bone marrow transplantation. Br. J. Haematol. 121, 597–604.
Middleton, P. G., Taylor, P. R., Jackson, G., Proctor, S. J., and Dickinson, A. M. (1998) Cytokine gene polymorphisms associating with severe acute graft-versus-host disease in HLA-identical sibling transplants. Blood 92, 3943–3948.
Rocha, V., Franco, R. F., Porcher, R., et al. (2002) Host defense and inflammatory gene polymorphisms are associated with outcomes after HLA-identical sibling bone marrow transplantation. Blood 100, 3908–3918.
Socie, G., Loiseau, P., Tamouza, R., et al. (2001) Both genetic and clinical factors predict the development of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Transplantation 72, 699–706.
Stark, G. L., Dickinson, A. M., Jackson, G. H., Taylor, P. R., Proctor, S. J., and Middleton, P. G. (2003) Tumour necrosis factor receptor type II196M/R genotype correlates with circulating soluble receptor levels in normal subjects and with graft-versus-host disease after sibling allogeneic bone marrow transplantation. Transplantation 76, 1742–1749.
Middleton, P. G., Cullup, H., Dickinson, A. M., et al. (2002) Vitamin D receptor gene polymorphism associates with graft-versus-host disease and survival in HLA-matched sibling allogeneic bone marrow transplantation. Bone Marrow Transplant 30, 223–228.
Middleton, P. G., Norden, J., Cullup, H., et al. (2003) Oestrogen receptor alpha gene polymorphism associates with occurrence of graft-versus-host disease and reduced survival in HLA-matched sib-allo BMT. Bone Marrow Transplant 32, 41–47.
Mullighan, C. G., Heatley, S., Doherty, K., et al. (2002) Mannose-binding lectin gene polymorphisms are associated with major infection following allogeneic hemopoietic stem cell transplantation. Blood 99, 3524–3529.
Mullighan, C., Heatley, S., Doherty, K., et al. (2004) Non-HLA immunogenetic polymorphisms and the risk of complications after allogeneic hemopoietic stemcell transplantation. Transplantation 77, 587–596.
Doney, K., Hagglund, H., Leisenring, W., Chauncey, T., Appelbaum, F. R., and Storb, R. (2003) Predictive factors for outcome of allogeneic hematopoietic cell transplantation for adult acute lymphoblastic leukaemia. Biol. Blood Marrow Transplant 9, 472–481.
Gratwohl, A., Hermans, J., Goldman, J. M., et al. (1998) Risk assessment for patients with chronic myeloid leukaemia before allogeneic blood or marrow transplantation. Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Lancet 352, 1087–1092.
Diaconescu, R., Flowers, C. R., Storer, B., et al. (2004) Morbidity and mortality with nonmyeloablative compared with myeloablative conditioning before hematopoietic cell transplantation from HLA-matched related donors. Blood 104, 1550–1558.
Spielman, R. S., McGinnis, R. E., and Ewens, W. J. (1993) Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am. J. Hum. Genet. 52, 506–516.
Ghosh, S. and Collins, F. S. (1996) The geneticist’s approach to complex disease. Ann. Rev. Med. 47, 333–353.
(1999) Freely associating. Nat. Genet. 22, 1–2.
Brull, D. J., Montgomery, H. E., Sanders, J., et al. (2001) Interleukin-6 gene-174g;gt;c and-572g>c promoter polymorphisms are strong predictors of plasma interleukin-6 levels after coronary artery bypass surgery. Arterioscler. Thromb. Vase. Biol. 21, 1458–1463.
Fishman, D., Faulds, G., Jeffery, R., et al. (1998) The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J. Clin. Invest. 102, 1369–1376.
Jones, K. G., Brull, D. J., Brown, L. C., et al. (2001) Interleukin-6 (IL-6) and the prognosis of abdominal aortic aneurysms. Circulation 103, 2260–2265.
Pravica, V., Asderakis, A., Perrey, C., Hajeer, A., Sinnott, P. J., and Hutchinson, I. V. (1999) In vitro production of IFN-gamma correlates with CA repeat polymorphism in the human IFN-gamma gene. Eur. J. Immunogenet 26, 1–3.
Pravica, V., Perrey, C., Stevens, A., Lee, J. H., and Hutchinson, I. V. (2000) A single nucleotide polymorphism in the first intron of the human IFN-gamma gene: absolute correlation with a polymorphic CA microsatellite marker of high IFN-gamma production. Hum. Immunol. 61, 863–866.
Rossouw, M., Nel, H. J., Cooke, G. S., van Helden, P. D., and Hoal, E. G. (2003) Association between tuberculosis and a polymorphic NFkappaB binding site in the interferon gamma gene. Lancet 361, 1871–1872.
Nejentsev, S., Godfrey, L., Snook, H., et al. (2004) Comparative high-resolution analysis of linkage disequilibrium and tag single nucleotide polymorphisms between populations in the vitamin D receptor gene. Hum. Mol. Genet. 13, 1633–1639.
London, S. J., Lehman, T. A., and Taylor, J. A. (1997) Myeloperoxidase genetic polymorphism and lung cancer risk. Cancer Res. 57, 5001–5003.
Wilson, A. G., di Giovine, F. S., Blakemore, A. I., and Duff, G. W. (1992) Single base polymorphism in the human tumour necrosis factor alpha (TNF alpha) gene detectable by Ncol restriction of PCR product. Hum. Mol. Genet. 1, 353.
Orita, M., Iwahana, H., Kanazawa, H., Hayashi, K., and Sekiya, T. (1989) Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms. Proc. Natl. Acad. Sci. USA 86, 2766–2770.
Glavac, D. and Dean, M. (1993) Optimization of the single-strand conformation polymorphism (SSCP) technique for detection of point mutations. Hum. Mutat. 2, 404–414.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2007 Humana Press Inc.
About this protocol
Cite this protocol
Middleton, P.G. (2007). Non-HLA Gene Polymorphisms in Stem Cell Transplantation. In: Beksac, M. (eds) Bone Marrow and Stem Cell Transplantation. Methods in Molecular Medicine, vol 134. Humana Press. https://doi.org/10.1007/978-1-59745-223-6_8
Download citation
DOI: https://doi.org/10.1007/978-1-59745-223-6_8
Publisher Name: Humana Press
Print ISBN: 978-1-58829-595-8
Online ISBN: 978-1-59745-223-6
eBook Packages: Springer Protocols