title: Genetic polymorphisms and bronchiolitis obliterans syndrome after lung transplantation:  promising results and recommendations for the future.
abstract: Survival rates after lung transplantation are the lowest among solid organ transplantations. Long-term survival is limited by the development of chronic rejection, known as bronchiolitis obliterans syndrome (BOS). Risk factors, such as acute rejection and cytomegalovirus infection, contribute to the development of BOS. However, these risk factors alone do not explain the interindividual variability seen in the development of BOS. There is growing evidence that genetic variations might contribute to an individual's susceptibility to rejection. In this systematic review, based on a literature search through Medline and Embase, an overview is given of the genetic polymorphisms that have been investigated in lung transplant recipients in relation to the devlopment of BOS. Functional genetic polymorphisms in the genes of IFNG (+874 A/T), TGFB1 (+915 G/C), and IL6 (-174 G/C) have been found to be associated with the development of BOS and allograft fibrosis after lung transplantation. However, confirmation was not consistent across all studied cohorts. Genetic polymorphisms in the genes of several Toll-like receptors, mannose-binding lectin, CD14, killer immunoglobulin-like receptors, and matrix metalloproteinase-7 were also found to be associated with the development of BOS, but these studies need to be replicated in independent cohorts. This review shows that there may be involvement of genetic polymorphisms in the development of BOS. Genetic risk profiling of lung transplant recipients could be a promising approach for the future, enabling individualized risk stratification and personalized immunosuppressive treatment after transplantation. Further studies are needed to define risk alleles.
authors.affiliation: Department of Pulmonology, Centre of Interstitial Lung Diseases, St Antonius Hospital, Nieuwegein, The Netherlands.
authors.forename: Elisabeth A
authors.initials: EA
authors.lastname: Kastelijn
authors.forename: Coline H M
authors.initials: CH
authors.lastname: van Moorsel
authors.forename: Henk J T
authors.initials: HJ
authors.lastname: Ruven
authors.forename: Jan-Willem J
authors.initials: JW
authors.lastname: Lammers
authors.forename: Jan C
authors.initials: JC
authors.lastname: Grutters
mesh_terms: D001989:Bronchiolitis Obliterans / Q000209:etiology* / Q000235:genetics* / Q000276:immunology; D016207:Cytokines / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007371:Interferon-gamma / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D016040:Lung Transplantation / Q000009:adverse effects* / Q000276:immunology; D008297:Male; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013577:Syndrome; D053773:Transforming Growth Factor beta1 / Q000235:genetics
chemical_list: D016207:Cytokines; C508600:IL6 protein, human; D015850:Interleukin-6; D053773:Transforming Growth Factor beta1; D007371:Interferon-gamma