title: Association of SORL1 alleles with late-onset Alzheimer's disease. findings from the GIGAS_LOAD study and mega-analysis.
abstract: The pathophysiology of Alzheimer's disease (AD) is influenced by sorting-protein related receptor (sorLa) that is less expressed in AD patients. The gene encoding sorLa (SORL1) has been investigated as a susceptibility factor for late-onset AD (LOAD) with conflicting results. Our objectives were to confirm the association between SORL1 SNPs and LOAD in two independent South-European centers and to perform a mega-analysis of published samples. We analyzed three SORL1 SNPs (intron 6: rs668387; rs689021; rs641120) from the Greece-Italy Genetic Association Study on lateonset AD (GIGAS_LOAD). Greek sample included 96 patients with LOAD (DSM-IV) and 120 unrelated controls. In Italy, a community-based sample is ongoing. 47 LOAD patients and 165 controls were recruited until study endpoint. These samples and previously published ones (Alzgene) were pooled as in a single study. A test for trend was used to analyze genotype association. In the GIGAS_LOAD sample no association was detected between SORL1 genotypes and LOAD. Conversely all SNPs were associated with LOAD in mega-analysis based on ordinal classification of genotypes (Armitage's test: p < 0.001). Although our analysis of pooled samples has positive results for the association between SORL1 and AD, there is substantial heterogeneity across studies. Thus further examination into SORL1 SNPs and the population is necessary to determine the role of SORL1 in LOAD.
authors: Institute of Psychiatry, University of Bologna, Bologna, Italy.
authors: Paolo
authors: P
authors: Olgiati
authors: Antonis
authors: A
authors: Politis
authors: Diego
authors: D
authors: Albani
authors: Serena
authors: S
authors: Rodilossi
authors: Letizia
authors: L
authors: Polito
authors: Eleonora
authors: E
authors: Ateri
authors: Aikaterini
authors: A
authors: Zisaki
authors: Christina
authors: C
authors: Piperi
authors: Ioannis
authors: I
authors: Liappas
authors: Evangelia
authors: E
authors: Stamouli
authors: Antonis
authors: A
authors: Mailis
authors: Anna R
authors: AR
authors: Atti
authors: Barbara
authors: B
authors: Ferrari
authors: Valentina
authors: V
authors: Morini
authors: Francesca
authors: F
authors: Moretti
authors: Gloria
authors: G
authors: Biella
authors: Gianluigi
authors: G
authors: Forloni
authors: George N
authors: GN
authors: Papadimitriou
authors: Diana De
authors: DD
authors: Ronchi
authors: Anastasios
authors: A
authors: Kalofoutis
authors: Alessandro
authors: A
authors: Serretti
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006115:Greece; D006801:Humans; D007391:International Cooperation; D007558:Italy; D026502:LDL-Receptor Related Proteins / Q000235:genetics*; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D026502:LDL-Receptor Related Proteins; D026901:Membrane Transport Proteins; C102582:SORL1 protein, human