A single nucleotide polymorphism in the first intron of the human IFN-gamma gene: Absolute correlation with a polymorphic CA microsatellite marker ofhigh IFN-gamma production

We have described previously a variable length CA repeat sequence in the Fi rst intron of the human IFN-gamma gene and showed that allele #2 is associa ted with high in vitro IFN-gamma production. In a consecutive study, allele #2 was found to be associated with allograft fibrosis in lung transplant p atients, confirming its role as a marker of high IFN-gamma production, both in vivo and in vitro. In this study we have sequenced 50 PCR products that had been typed previously by PAGE for the identification of CA microsatell ite alleles. We report on a novel single nucleotide polymorphism, T co A, a t the 5' end of the CA repeat region in the first intron of the human IFN-g amma gene (+874*T/A). There is an absolute correlation between the presence of T allele and the presence of the high-producing microsatellite allele # 2. This T to A polymorphism coincides with a putative NF-kappaB binding sit e which might have functional consequences for the transcription of the hum an IFN-gamma gene. Therefore, the T to A polymorphism could directly influe nce the level of IFN-gamma production associated with the CA microsatellite marker. Human Immunology 61, 863-866 (2000). (C) American Society for Hist ocompatibility and Immunogenetics, 2000. Published by Elsevier Science Inc.