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Genetic study of neurexin and neuroligin genes in Alzheimer's disease.
- Source :
-
Journal of Alzheimer's disease : JAD [J Alzheimers Dis] 2013; Vol. 35 (2), pp. 403-12. - Publication Year :
- 2013
-
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.
- Subjects :
- Alzheimer Disease epidemiology
Calcium-Binding Proteins
Cell Adhesion Molecules, Neuronal genetics
DNA genetics
DNA isolation & purification
Databases, Genetic
Genetic Markers
Genome-Wide Association Study
Genotype
Haplotypes
Humans
Linkage Disequilibrium
Neural Cell Adhesion Molecules
Polymorphism, Single Nucleotide genetics
Sex Characteristics
Spain epidemiology
White People
Alzheimer Disease genetics
Nerve Tissue Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1875-8908
- Volume :
- 35
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of Alzheimer's disease : JAD
- Publication Type :
- Academic Journal
- Accession number :
- 23403532
- Full Text :
- https://doi.org/10.3233/JAD-122257