CA repeat allele polymorphism in the first intron of the human interferon-gamma gene is associated with lung allograft fibrosis

Interferon-gamma (IFN-gamma) is an inflammatory cytokine that has been impl icated in the development of fibrosis in inflamed tissues. In this study we have analysed the association between genetically-determined high IFN-gamm a production and development of fibrosis in lung transplants. The human IFN -gamma gene has a variable length CA repeat in the first intron. Our previo us study showed that polymorphism of this microsatellite is associated with individual variation in the levels of IFN-gamma production. In vitro produ ction of IFN-gamma showed significant correlation with presence of allele # 2 (p < 0.01). In this study allele #2 was found to be associated with allog raft fibrosis defined by transbronchial biopsy. An analysis of two groups o f lung transplant recipient study showed a significant increase in the freq uency of allele #2 in the group which developed fibrosis after transplantat ion compared to the group that did not (p < 0.005). We postulate that the p roduction of IFN-gamma, which is under genetic control, can influence the d evelopment of fibrosis in lung allografts. Human Immunology 60, 343-346 (19 99). (C) American Society for Histocompatibility and Immunogenetics, 1999 P ublished by Elsevier Science Inc.