title: Genetic variations in tau-tubulin kinase-1 are linked to Alzheimer's disease in a Spanish case-control cohort.
abstract: 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.
authors.affiliation: Neurology Service and CIBERNED, Marqués de Valdecilla University Hospital, University of Cantabria, Avda. Valdecilla, 39008 Santander, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Vázquez-Higuera
authors.forename: Ana
authors.initials: A
authors.lastname: Martínez-García
authors.forename: Pascual
authors.initials: P
authors.lastname: Sánchez-Juan
authors.forename: Eloy
authors.initials: E
authors.lastname: Rodríguez-Rodríguez
authors.forename: Ignacio
authors.initials: I
authors.lastname: Mateo
authors.forename: Ana
authors.initials: A
authors.lastname: Pozueta
authors.forename: Ana
authors.initials: A
authors.lastname: Frank
authors.forename: Fernando
authors.initials: F
authors.lastname: Valdivieso
authors.forename: José
authors.initials: J
authors.lastname: Berciano
authors.forename: María J
authors.initials: MJ
authors.lastname: Bullido
authors.forename: Onofre
authors.initials: O
authors.lastname: Combarros
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics; D016009:Chi-Square Distribution; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D013030:Spain / Q000453:epidemiology
chemical_list: D053327:Apolipoprotein E4; C095903:tau-tubulin kinase; D017346:Protein Serine-Threonine Kinases