title: Genetic study of neurexin and neuroligin genes in Alzheimer's disease.
abstract: The interaction between neurexins and neuroligins promotes the formation of functional synaptic structures. Recently, it has been reported that neurexins and neuroligins are proteolytically processed by presenilins at synapses. Based on this interaction and the role of presenilins in familial Alzheimer's disease (AD), we hypothesized that dysfunction of the neuroligin-neurexin pathway might be associated with AD. To explore this hypothesis, we carried out a meta-analysis of five genome-wide association studies (GWAS) comprising 1, 256 SNPs in the NRXN1, NRXN2, NRXN3, and NLGN1 genes (3,009 cases and 3,006 control individuals). We identified a marker in the NRXN3 gene (rs17757879) that showed a consistent protective effect in all GWAS, however, the statistical significance obtained did not resist multiple testing corrections (OR = 0.851, p = 0.002). Nonetheless, gender analysis revealed that this effect was restricted to males. A combined meta-analysis of the former five GWAS together with a replication Spanish sample consisting of 1,785 cases and 1,634 controls confirmed this observation (rs17757879, OR = 0.742, 95% CI = 0.632-0.872, p = 0.00028, final meta-analysis). We conclude that NRXN3 might have a role in susceptibility to AD in males.
authors: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Spain.
authors: Amalia
authors: A
authors: Martinez-Mir
authors: Antonio
authors: A
authors: González-Pérez
authors: Javier
authors: J
authors: Gayán
authors: Carmen
authors: C
authors: Antúnez
authors: Juan
authors: J
authors: Marín
authors: Mercé
authors: M
authors: Boada
authors: Jesús María
authors: JM
authors: Lopez-Arrieta
authors: Evaristo
authors: E
authors: Fernández
authors: Reposo
authors: R
authors: Ramírez-Lorca
authors: María Eugenia
authors: ME
authors: Sáez
authors: Agustín
authors: A
authors: Ruiz
authors: Francisco G
authors: FG
authors: Scholl
authors: Luis Miguel
authors: LM
authors: Real
mesh_terms: D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics*; D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D030541:Databases, Genetic; D005819:Genetic Markers; D055106:Genome-Wide Association Study; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D009419:Nerve Tissue Proteins / Q000235:genetics*; D019006:Neural Cell Adhesion Molecules; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012727:Sex Characteristics; D013030:Spain / Q000453:epidemiology; D044465:White People
chemical_list: D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal; D005819:Genetic Markers; C539628:NRXN1 protein, human; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; C093175:neurexin II; C082354:neurexin IIIalpha; C093438:neuroligin 1; D004247:DNA