Cruchaga Carlos, Vidal-Taboada Jose M, Ezquerra Mario, Lorenzo Elena, Martinez-Lage Pablo, Blazquez Marta, Tolosa Eduardo, Pastor Pau
Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona, Spain.
Neurobiol Dis. 2009 Feb;33(2):164-70. doi: 10.1016/j.nbd.2008.09.027. Epub 2008 Nov 1.
Two different H1 sub-haplotypes at chromosome 17q21, H1C and H1E'A, have been associated with progressive supranuclear palsy (PSP) and cortical basal degeneration (CBD). We analyzed the SNPs included in the H1C and H1E'A haplotypes in a large Spanish PSP/CBD series and their interaction with age at onset (AAO). Survival analysis of rs1880753 marker was consistently associated with disease risk and with an earlier age at onset under an additive model. Its location at 160 kb and 50 kb upstream of tau and CRHR1 genes, respectively, suggests that it might act as a cis-element that regulates gene expression. Rs45502095(H1) was also associated with AAO under a recessive model. Haplotype analysis failed to replicate the association of H1C and H1E'A haplotypes with PSP/CBD. However, we found a strong association of two H1 sub-haplotypes with PSP and CBD (H1E'C and H1Q), which include MAPT and CRHR1 genes where the risk variant for PSP/CBD could lie.
位于17号染色体q21区域的两种不同的H1单倍型，即H1C和H1E'A，与进行性核上性麻痹（PSP）和皮质基底节变性（CBD）相关。我们在一个大型西班牙PSP/CBD队列中分析了H1C和H1E'A单倍型中包含的单核苷酸多态性（SNP）及其与发病年龄（AAO）的相互作用。rs1880753标记的生存分析在加性模型下始终与疾病风险和较早的发病年龄相关。它分别位于tau基因和促肾上腺皮质激素释放激素受体1（CRHR1）基因上游160 kb和50 kb处，这表明它可能作为一种顺式元件调节基因表达。rs45502095（H1）在隐性模型下也与发病年龄相关。单倍型分析未能重复H1C和H1E'A单倍型与PSP/CBD的关联。然而，我们发现两种H1亚单倍型与PSP和CBD（H1E'C和H1Q）有很强的关联，这两种亚单倍型包含PSP/CBD风险变异可能所在的微管相关蛋白tau（MAPT）基因和CRHR1基因。
