Ezquerra M, Pastor P, Valldeoriola F, Molinuevo J L, Blesa R, Tolosa E, Oliva R
Genetics Service, Hospital Clínic i Provincial, Faculty of Medicine, University of Barcelona, Institut d'lnvestigacions Biomèdiques August Pi y Sunyer, Spain.
Neurosci Lett. 1999 Nov 19;275(3):183-6. doi: 10.1016/s0304-3940(99)00738-7.
An intronic polymorphism and other changes in the transcribed region of the tau gene forming a haplotype have been previously described associated to progressive supranuclear palsy (PSP). These results raised the possibility that a change at or near the tau gene could be responsible for an increased risk to develop PSP. We initiated the present work in research for potential changes in the promoter region of the tau gene that could further extend the previously described haplotype. The tau promoter region was analyzed through single strand conformation polymorphism followed by direct sequencing in PSP patients (n = 35), in controls (n = 195) and in Alzheimer's disease (AD; n = 74) patients. We have been able to identify a G to C change at position -221 of the tau gene promoter region. The CC genotype has been detected to be present with a significantly higher frequency in PSP patients (91.4%; P < 0.00001; OR = 11.8), but not in AD patients, as compared with controls (49.74%). Subsequently we have detected that the CC -221 tau promoter genotype is significantly associated to the tau intronic A0/A0 genotype (P < 0.00001). The detected -221 tau G to C change occurs within a potential c-myb proto-oncogene element present in the promoter region. Thus, in addition to extending the previously described haplotype associated to PSP, this -221 G to C change is an interesting candidate that could provide a potential explanation for the association of the haplotype to increased risk for developing PSP.
先前已描述，tau基因转录区域中的内含子多态性及其他变化形成单倍型，与进行性核上性麻痹（PSP）相关。这些结果提示，tau基因处或其附近的变化可能是导致PSP发病风险增加的原因。我们开展了本研究，以探寻tau基因启动子区域中可能进一步扩展先前所述单倍型的潜在变化。通过单链构象多态性分析，随后对PSP患者（n = 35）、对照者（n = 195）和阿尔茨海默病（AD；n = 74）患者进行直接测序，对tau基因启动子区域进行了分析。我们在tau基因启动子区域的 -221位点发现了一个G到C的变化。与对照者（49.74%）相比，CC基因型在PSP患者中出现的频率显著更高（91.4%；P < 0.00001；OR = 11.8），但在AD患者中并非如此。随后我们检测到，CC -221 tau启动子基因型与tau基因内含子A0/A0基因型显著相关（P < 0.00001）。检测到的tau基因 -221位点G到C的变化发生在启动子区域存在的一个潜在c-myb原癌基因元件内。因此，除了扩展先前所述的与PSP相关的单倍型外，这种 -221 G到C的变化是一个有趣的候选因素，它可能为该单倍型与PSP发病风险增加之间的关联提供潜在解释。
