rs5848 polymorphism and serum progranulin level.
rs5848 polymorphism and serum progranulin level.
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DOI：
10.1016/j.jns.2010.10.009
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发表时间：
2011-01-15
影响因子：
4.4
通讯作者：
Mackenzie, Ian R. A.
中科院分区：
文献类型：
--
作者：
Hsiung, Ging-Yuek R.;Fok, Alice;Feldman, Howard H.;Rademakers, Rosa;Mackenzie, Ian R. A.
评估rs 5848多态性对来自三级转诊诊所的阿尔茨海默病和相关痴呆受试者队列中血清颗粒蛋白前体（PGRN）水平的影响。GRN基因突变通过单倍不足导致常染色体显性额颞叶痴呆（FTD）伴TDP-43病理（FTLD-TDP）。最近的研究表明，rs 5848 T等位基因的纯合子携带者发生FTD的风险升高，该多态性可能通过改变颗粒蛋白前体水平在其他痴呆的发病机制中发挥作用。我们假设rs 5848基因型可能影响AD、FTD和其他痴呆患者的血清PGRN水平。血液样品从被转诊到三级痴呆诊所的患有认知障碍和痴呆的患者获得，以及来自健康对照组的样品。使用ELISA测定法测量血清PGRN水平，并通过TaqMan测定法确定rs 5848基因型。发现rs 5848 SNP对血清PGRN水平有显著影响，TT基因型PGRN水平最低，CC基因型最高。在每个亚组中均观察到这种关系。我们还证实了GRN突变携带者的血清PGRN水平显著低于所有其他组。rs 5848多态性显著影响血清PGRN，TT携带者血清PGRN水平低于CT和CC携带者。这与miR-659与rs 5848的高风险T等位基因结合可能增强GRN的翻译抑制并改变FTD和可能的其他痴呆风险的发现一致。
To assess the influence of rs5848 polymorphism in serum progranulin (PGRN) level in a cohort of subjects with Alzheimer and related dementias from a tertiary referral clinic. Mutations in the GRN gene cause autosomal dominant frontotemporal dementia (FTD) with TDP-43 pathology (FTLD-TDP) through haploinsufficiency. It has recently been shown that homozygous carriers of the T-allele of rs5848 have an elevated risk developing FTD, and this polymorphism may play a role in the pathogenesis of other dementia by modifying progranulin level. We hypothesize that genotype of rs5848 may influence serum PGRN level in AD, FTD, and other dementias. Blood samples were obtained from patients with cognitive impairment and dementia referred to a tertiary dementia clinic, as well as samples from a cohort of healthy controls. Serum PGRN level was measured using an ELISA assay, and rs5848 genotype was determined by a TaqMan assay. We found that rs5848 SNP significantly influenced serum PGRN level, with TT genotype having the lowest levels, CC the highest. This relationship is observed in each of the subgroups. We also confirmed that GRN mutation carriers had significantly lower serum PGRN levels than all other groups. The rs5848 polymorphism significantly influences serum PGRN with TT carriers having a lower level of serum PGRN then CT and CC carriers. This is consistent with the finding that miR-659 binding to the high risk T allele of rs5848 may augment translational inhibition of GRN and alter risk of FTD and possibly other dementias.
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影响因子：
64.8
作者：
Cruts, Marc;Gijselinck, Ilse;Van Broeckhoven, Christine
通讯作者：
Van Broeckhoven, Christine
影响因子：
8
作者：
Tolkatchev, Dmitri;Malik, Suneil;Ni, Feng
通讯作者：
Ni, Feng
影响因子：
4.2
作者：
Rollinson, Sara;Rohrer, Jonathan D.;Pickering-Brown, Stuart M.
通讯作者：
Pickering-Brown, Stuart M.
血清前植物浓度可能与巨噬细胞浸润到胶质脂肪组织中。
影响因子：
7.7
作者：
Youn BS;Bang SI;Klöting N;Park JW;Lee N;Oh JE;Pi KB;Lee TH;Ruschke K;Fasshauer M;Stumvoll M;Blüher M
通讯作者：
Blüher M
影响因子：
4.8
作者：
Mackenzie IR;Rademakers R
通讯作者：
Rademakers R