Genetic variations in tau-tubulin kinase-1 are linked to Alzheimer's disease in a Spanish case-control cohort

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• 作者：José ; Luis Vá ; zquez-Higuera^a ; Ana Martí ; nez-Garcí ; a^b ; Pascual Sá ; nchez-Juan^a ; Eloy Rodrí ; guez-Rodrí ; guez^a ; Ignacio Mateo^a ; Ana Pozueta^a ; Ana Frank^c ; Fernando Valdivieso^b ; José ; Berciano^a ; Marí ; a J. Bullido^b ; Onofre Combarros^a ; ^{combarro@unican.es}
• 关键词：Alzheimer's disease ; Tau-tubulin kinase-1 ; Tau phosphorylation ; Genetic polymorphism
• 刊名：Neurobiology of Aging
• 出版年：2011
• 出版时间：March 2011
• 年：2011
• 卷：32
• 期：3
• 页码：550.e5-550.e9
• 全文大小：317 K

文摘

Neurofibrillary tangles, one of the characteristic neuropathological lesions found in Alzheimer's disease (AD) brains, are composed of abnormally hyperphosphorylated tau protein. Tau-tubulin kinase-1 (TTBK1) is a brain-specific protein kinase involved in tau phosphorylation at AD-related sites. We examined genetic variations of TTBK1 by genotyping nine haplotype tagging SNPs (htSNPs) (rs2104142, rs2651206, rs10807287, rs7764257, rs3800294, rs1995300, rs2756173, rs6936397, and rs6458330) in a group of 645 Spanish late-onset AD patients and 738 healthy controls. Using a recessive genetic model, minor allele homozygotes for rs2651206 in intron 1 (OR = 0.50, p = 0.0003), rs10807287 in intron 5 (OR = 0.49, p = 0.0002), and rs7764257 in intron 9 (OR = 0.57, p = 0.023), which are in strong linkage disequilibrium, had a lower risk of developing AD than subjects homozygotes and heterozygotes for the major allele. TTBK1 is a promising new candidate tau phosphorylation-related gene for AD risk.