Pravica V, Perrey C, Stevens A, Lee J H, Hutchinson I V
School of Biological Sciences, University of Manchester, Manchester, United Kingdom.
Hum Immunol. 2000 Sep;61(9):863-6. doi: 10.1016/s0198-8859(00)00167-1.
We have described previously a variable length CA repeat sequence in the first intron of the human IFN-gamma gene and showed that allele #2 is associated with high in vitro IFN-gamma production. In a consecutive study, allele #2 was found to be associated with allograft fibrosis in lung transplant patients, 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 microsatellite alleles. We report on a novel single nucleotide polymorphism, T to A, at the 5' end of the CA repeat region in the first intron of the human IFN-gamma 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-kappa B binding site which might have functional consequences for the transcription of the human IFN-gamma gene. Therefore, the T to A polymorphism could directly influence the level of IFN-gamma production associated with the CA microsatellite marker.
我们之前已经描述过人干扰素-γ基因第一内含子中的可变长度CA重复序列，并表明等位基因#2与体外高干扰素-γ产生相关。在一项连续研究中，发现等位基因#2与肺移植患者的同种异体移植纤维化相关，证实了其作为体内和体外高干扰素-γ产生标志物的作用。在本研究中，我们对50个先前通过聚丙烯酰胺凝胶电泳（PAGE）分型以鉴定CA微卫星等位基因的PCR产物进行了测序。我们报告了人干扰素-γ基因第一内含子CA重复区域5'端（+874*T/A）的一个新的单核苷酸多态性，即T到A。T等位基因的存在与高产微卫星等位基因#2的存在之间存在绝对相关性。这种T到A多态性与一个假定的核因子κB结合位点重合，这可能对人干扰素-γ基因的转录产生功能影响。因此，T到A多态性可能直接影响与CA微卫星标记相关的干扰素-γ产生水平。
