title: The RELN locus in Alzheimer's disease.
abstract: Reelin, a serine protease encoded by the RELN gene, is part of the apolipoprotein E (apoE) biochemical pathway that is involved in the pathogenesis of Alzheimer's disease (AD). Sex-related differences in the epidemiology, pathology and clinical characteristics of AD have been reported. To explore the potential contribution of RELN gene variants in the pathogenesis of AD, we investigated three polymorphisms spanning the RELN locus, i.e., a triplet tandem repeat in the 5'UTR and two single-nucleotide polymorphisms (SNPs) rs607755 and rs2229874, located in the splice-junction of exon 6 and in the coding region of exon 50. The analysis was made in 223 sporadic AD patients and 181 age-matched controls of Caucasian ethnicity. Significant differences between AD patients and controls were found in distribution of 5'UTR and rs607755 genotypes, whereas no differences were found in the distribution of rs2229874 genotypes. When patients and controls were divided according to sex, significant differences in genotype distribution were found in females and not in males, also after adjustment for APOE genotypes. These findings suggest that RELN gene variants may play a role in the pathogenesis of AD, particularly in females.
authors.affiliation: Geriatric Unit & Gerontology-Geriatric Research Laboratory, Department of Medical Sciences, I.R.C.C.S. Casa Sollievo dalla Sofferenza, San Giovanni Rotondo (FG), I-71013, Italy. dseripa@operapadrepio.it
authors.forename: Davide
authors.initials: D
authors.lastname: Seripa
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Matera
authors.forename: Marilisa
authors.initials: M
authors.lastname: Franceschi
authors.forename: Antonio
authors.initials: A
authors.lastname: Daniele
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bizzarro
authors.forename: Monica
authors.initials: M
authors.lastname: Rinaldi
authors.forename: Francesco
authors.initials: F
authors.lastname: Panza
authors.forename: Vito Michele
authors.initials: VM
authors.lastname: Fazio
authors.forename: Carolina
authors.initials: C
authors.lastname: Gravina
authors.forename: Grazia
authors.initials: G
authors.lastname: D'Onofrio
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Solfrizzi
authors.forename: Carlo
authors.initials: C
authors.lastname: Masullo
authors.forename: Alberto
authors.initials: A
authors.lastname: Pilotto
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D004274:DNA, Recombinant / Q000235:genetics; D005091:Exons / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000235:genetics*
chemical_list: D001057:Apolipoproteins E; D015816:Cell Adhesion Molecules, Neuronal; D004274:DNA, Recombinant; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717127:RELN protein, human; D012697:Serine Endopeptidases