title: Septin 3 gene polymorphism in Alzheimer's disease.
abstract: Septin 3 is a novel member of the septin subfamily of GTPase domain proteins that was recently identified in human neuronal cells. These proteins are involved in vesicle trafficking, neurite outgrowth, and neurofibrillary tangle formation; however, the expression and functional role of septin 3 in normal neuronal tissues and as an etiological agent in neurological disorders is currently unclear. To further characterize these parameters, the present study analyzed the expression of three isoforms of septin 3 (A, B, and C) in fetal and adult human brains and polymorphism of the septin 3 exon 11 microsatellite in control, pure Alzheimer's disease (AD), Lewy body variant (LBV) of AD, and Parkinson's disease. Septin 3 mRNAs for isoforms A and B, but not C, were detected in the frontal cortex of fetus and adult human samples, as measured by reverse transcription-coupled polymerase chain reaction. Genotype analyses indicated that polymorphic septin 3 alleles were distributed in two peaks of frequency in both control and disease groups. Categorization of the alleles into short (S) and long (L) types revealed a significant difference between AD patients and controls (p = 0.034 by chi-square test). Furthermore, the S-allele homozygosity was significantly underrepresented in AD compared with control (p = 0.015 by chi-square test). These results suggest that polymorphism in exon 11 of septin 3 may have a determinative role in the pathogenesis of AD.
authors.affiliation: Laboratory of Molecular Clinical Chemistry, Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Takehashi
authors.forename: Tyler
authors.initials: T
authors.lastname: Alioto
authors.forename: Todd
authors.initials: T
authors.lastname: Stedeford
authors.forename: Amanda S
authors.initials: AS
authors.lastname: Persad
authors.forename: Marek
authors.initials: M
authors.lastname: Banasik
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
authors.forename: Seigo
authors.initials: S
authors.lastname: Tanaka
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Ueda
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017398:Alternative Splicing / Q000235:genetics; D000544:Alzheimer Disease / Q000235:genetics*; D001923:Brain Chemistry / Q000235:genetics; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D005091:Exons / Q000235:genetics; D020558:GTP Phosphohydrolases / Q000235:genetics*; D015870:Gene Expression / Q000235:genetics; D005787:Gene Frequency; D006801:Humans; D020961:Lewy Body Disease / Q000235:genetics; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000032:analysis; D058112:Septins
chemical_list: D012333:RNA, Messenger; D019389:Cytochrome P-450 CYP2D6; D020558:GTP Phosphohydrolases; D058112:Septins; C407343:septin 3