A polymorphism in the tau gene associated with risk for Alzheimer's disease.
Searching for tau genetic variations which could be associated with risk for Alzheimer's disease (AD), we have performed a mutational analysis of a region containing the whole exon 11 of the tau gene, which encodes a microtubule binding region critical for tau self-assembly, and we have found a biallelic polymorphism at position +34 of intron 11 (IVS11 + 34G/A). We have analyzed the allelic frequencies of this polymorphism in a case-control sample (167 clinically diagnosed AD and 194 controls) and found that the presence of any G allele (genotypes AG + GG) is associated with a five-fold AD risk in individuals carrying the apolipoprotein E4 allele, strongly suggesting that the combined effect of tau and apoE is relevant in relation with AD pathogenesis.
Bullido
M J
MJ
Departamento de Biología Molecular and Centro de Biología Molecular Severo Ochoa (C.S.I.C.-U.A.M.), Universidad Autónoma de Madrid, Cantoblanco, Spain.
Aldudo
J
J
Frank
A
A
Coria
F
F
Avila
J
J
Valdivieso
F
F
D017668:Age of Onset; D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D001665:Binding Sites; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics; D008870:Microtubules / Q000378:metabolism; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D012307:Risk Factors; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D009419:Nerve Tissue Proteins; D016875:tau Proteins