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 implicated in the development of fibrosis in inflamed tissues. In this study we have analysed the association between genetically-determined high IFN-gamma production and development of fibrosis in lung transplants. The human IFN-gamma gene has a variable length CA repeat in the first intron. Our previous study showed that polymorphism of this microsatellite is associated with individual variation in the levels of IFN-gamma production. In vitro production 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 allograft fibrosis defined by transbronchial biopsy. An analysis of two groups of lung transplant recipients showed a significant increase in the frequency of allele #2 in the group which developed fibrosis after transplantation compared to the group that did not (p < 0.005). We postulate that the production of IFN-gamma, which is under genetic control, can influence the development of fibrosis in lung allografts.
Awad
M
M
School of Biological Sciences, University of Manchester, UK.
Pravica
V
V
Perrey
C
C
El Gamel
A
A
Yonan
N
N
Sinnott
P J
PJ
Hutchinson
I V
IV
D000225:Adenine; D000483:Alleles; D003596:Cytosine; D018900:Dinucleotide Repeats / Q000276:immunology*; D015870:Gene Expression / Q000276:immunology; D005787:Gene Frequency / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics*; D007438:Introns / Q000276:immunology*; D016040:Lung Transplantation / Q000009:adverse effects / Q000276:immunology* / Q000473:pathology; D011110:Polymorphism, Genetic / Q000276:immunology*; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000235:genetics* / Q000276:immunology*; D014184:Transplantation, Homologous
D007371:Interferon-gamma; D003596:Cytosine; D000225:Adenine