title: Reelin signaling pathway genotypes and Alzheimer disease in a Spanish population.
abstract: BACKGROUND
  Several reports suggest that the reelin protein could play a role in Alzheimer pathophysiology. This led us to ask whether genetic variability in the reelin pathway may increase the risk of developing Alzheimer disease (AD) or mild cognitive impairment (MCI).
  
  
  METHODS
  This was a case-control study in which neuropsychological tests were administered and peripheral blood samples taken. The study included 121 patients with AD, 94 with MCI, and 198 controls. Forty biallelic variants single nucleotide polimorphisms were genotyped in 8 genes related to reelin signaling pathway using a SNPlex genotyping system, and allele frequencies were compared between patients and controls using χ tests and obtaining odds ratios (OR).
  
  
  RESULTS
  A total of 413 subjects with complete neuropsychological data were analyzed. A significant association between the genotypes RELN (rs528528 and rs2299356), PLK2 (rs15009 and rs702723), and CAMK2A (rs3756577 and rs3822606) and AD or MCI was found. A significant association also was found between the GG genotype at the RELN-rs2299356 and the risk of AD (OR=2.68, P=0.003) and between the AG genotype at the CAMK2A-rs3822606 (OR=2.13, P=0.004). We found a protective effect of the RELN-rs528528 CT genotype and MCI (OR=0.36, P=0.002), and the PLK2-rs15009 CC and GG genotypes and CC genotype at PLK2-rs702723 with OR ranging from 0.40 to 0.57 on AD. These data suggest that TT or CT genotypes at CAMK2A-rs3756577 is associated with risk reduction for AD and MCI ranging from 2 to nearly 8 times.
  
  
  CONCLUSIONS
  Our data suggest a possible relation between certain reelin signaling pathway genotypes and cognitive impairment related to AD.
authors.affiliation: Departments of *Neurology †Clinical Epidemiology and Research, Vic General Hospital, Vic Departments of ‡Neurology §Cardiology ∥Epidemiology and Public Health, Hospital de la Santa Creu i Sant Pau, Barcelona ¶Bernades Geriatric Center, Manresa, Spain.
authors.forename: Enric
authors.initials: E
authors.lastname: Bufill
authors.forename: Pere
authors.initials: P
authors.lastname: Roura-Poch
authors.forename: Isabel
authors.initials: I
authors.lastname: Sala-Matavera
authors.forename: Sofía
authors.initials: S
authors.lastname: Antón
authors.forename: Alberto
authors.initials: A
authors.lastname: Lleó
authors.forename: Belén
authors.initials: B
authors.lastname: Sánchez-Saudinós
authors.forename: Lluís
authors.initials: L
authors.lastname: Tomàs-Abadal
authors.forename: Teresa
authors.initials: T
authors.lastname: Puig
authors.forename: Josep
authors.initials: J
authors.lastname: Abós
authors.forename: Santiago
authors.initials: S
authors.lastname: Bernades
authors.forename: Jordi
authors.initials: J
authors.lastname: Clarimon
authors.forename: Rafael
authors.initials: R
authors.lastname: Blesa
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics* / Q000523:psychology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics*; D016022:Case-Control Studies; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D060825:Cognitive Dysfunction / Q000235:genetics* / Q000523:psychology; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D013030:Spain
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C496126:PLK2 protein, human; D017346:Protein Serine-Threonine Kinases; C517657:CAMK2A protein, human; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; C000717127:RELN protein, human; D012697:Serine Endopeptidases