BACKGROUND: Existing data indicate that non-human leukocyte antigen (HLA) immunogenetic polymorphisms influence the risk of complications after allogeneic hemopoietic stem-cell transplantation. However, prior studies have been limited by small sample size and limited genotyping. METHODS: We examined 22 polymorphisms in 11 immunoregulatory genes including cytokines, mediators of apoptosis, and host-defense molecules by polymerase chain reaction using sequence-specific primers in 160 related myeloablative transplants. Associations were confirmed in two independent cohorts. RESULTS: An intronic polymorphism in the tumor necrosis factor gene (TNF 488A) was associated with the risk of acute graft-versus-host disease (GVHD) (odds ratio [OR] 16.9), grades II to IV acute GVHD (OR 3.3), chronic GVHD (OR 12.5), and early death posttransplant (OR 3.4). Recipient Fas -670G and donor interleukin (IL)-6 -174G were independent risk factors for acute GVHD. Recipient IL-10 ATA and Fas -670 genotype were independent risk factors for chronic GVHD. Recipient IL-1beta +3953T was associated with hepatic acute GVHD, and Fas -670G was associated with major infection. CONCLUSIONS: These results highlight the potential importance of cytokine and apoptosis gene polymorphisms in stem-cell transplantation, and indicate that non-HLA genotyping may be useful to identify individuals at the highest risk of complications and new targets for therapeutic intervention.
BACKGROUND: Existing data indicate that non-human leukocyte antigen (HLA) immunogenetic polymorphisms influence the risk of complications after allogeneic hemopoietic stem-cell transplantation. However, prior studies have been limited by small sample size and limited genotyping. METHODS: We examined 22 polymorphisms in 11 immunoregulatory genes including cytokines, mediators of apoptosis, and host-defense molecules by polymerase chain reaction using sequence-specific primers in 160 related myeloablative transplants. Associations were confirmed in two independent cohorts. RESULTS: An intronic polymorphism in the tumor necrosis factor gene (TNF 488A) was associated with the risk of acute graft-versus-host disease (GVHD) (odds ratio [OR] 16.9), grades II to IV acute GVHD (OR 3.3), chronic GVHD (OR 12.5), and early death posttransplant (OR 3.4). Recipient Fas -670G and donorinterleukin (IL)-6 -174G were independent risk factors for acute GVHD. Recipient IL-10 ATA and Fas -670 genotype were independent risk factors for chronic GVHD. Recipient IL-1beta +3953T was associated with hepatic acute GVHD, and Fas -670G was associated with major infection. CONCLUSIONS: These results highlight the potential importance of cytokine and apoptosis gene polymorphisms in stem-cell transplantation, and indicate that non-HLA genotyping may be useful to identify individuals at the highest risk of complications and new targets for therapeutic intervention.
Authors: Jason W Chien; Xinyi Cindy Zhang; Wenhong Fan; Hongwei Wang; Lue Ping Zhao; Paul J Martin; Barry E Storer; Michael Boeckh; Edus H Warren; John A Hansen Journal: Blood Date: 2012-01-26 Impact factor: 22.113
Authors: Sophie Paczesny; Frances T Hakim; Joseph Pidala; Kenneth R Cooke; Julia Lathrop; Linda M Griffith; John Hansen; Madan Jagasia; David Miklos; Steven Pavletic; Robertson Parkman; Estelle Russek-Cohen; Mary E D Flowers; Stephanie Lee; Paul Martin; Georgia Vogelsang; Marc Walton; Kirk R Schultz Journal: Biol Blood Marrow Transplant Date: 2015-01-30 Impact factor: 5.742
Authors: John A Hansen; Effie W Petersdorf; Ming-Tseh Lin; Steven Wang; Jason W Chien; Barry Storer; Paul J Martin Journal: Immunol Res Date: 2008 Impact factor: 2.829
Authors: Paul J Martin; Wenhong Fan; Barry E Storer; David M Levine; Lue Ping Zhao; Edus H Warren; Mary E D Flowers; Stephanie J Lee; Paul A Carpenter; Michael Boeckh; Sangeeta Hingorani; Li Yan; Qiang Hu; Leah Preus; Song Liu; Stephen Spellman; Xiaochun Zhu; Marcelo Pasquini; Philip McCarthy; Daniel Stram; Xin Sheng; Loreall Pooler; Christopher A Haiman; Lara Sucheston-Campbell; Theresa Hahn; John A Hansen Journal: Blood Date: 2016-10-06 Impact factor: 22.113