title: Possible influence of a non-synonymous polymorphism located in the NGF precursor on susceptibility to late-onset Alzheimer's disease and mild cognitive impairment.
abstract: The complex network of neurotrophic factors is supposed to play a role in neurodegeneration, but the effect of variations in their coding genes on susceptibility to sporadic Alzheimer's disease is not established. The mature form of nerve growth factor (NGF) derives from a precursor, proNGF, which was recently discovered to exert crucial functions in brain. We designed a case-control association study to test the hypothesis as to whether polymorphisms located in the proNGF genomic region influence the liability to Alzheimer's disease and its prodromal form, mild cognitive impairment. Three independent case-control samples, with individuals aged >60 years, were collected in Italian Alzheimer Units. One polymorphism located in the proNGF region, rs6330, demonstrated a minor allele frequency >5% and was used in the association study. The minor allele of rs6330 was more frequent in patients from the three sample series as compared to respective normal controls. Multivariate logistic regression showed a significant association under the dominant model in one cohort (OR 1.83, 95% CI 1.00-3.54) and in the pooled case-control sample (OR 1.47, 95% CI 1.03-2.08). These findings further suggest that proNGF may play a role in Alzheimer-type neurodegeneration and that genetic variations in the NGF locus may influence the occurrence of sporadic, late-onset Alzheimer's disease.
authors.affiliation: Department of Health Sciences, University of Genova, Genova, Italy. emilio.dimaria@unige.it
authors.forename: Emilio
authors.initials: E
authors.lastname: Di Maria
authors.forename: Elisa
authors.initials: E
authors.lastname: Giorgio
authors.forename: Vera
authors.initials: V
authors.lastname: Uliana
authors.forename: Cristian
authors.initials: C
authors.lastname: Bonvicini
authors.forename: Francesca
authors.initials: F
authors.lastname: Faravelli
authors.forename: Sergio
authors.initials: S
authors.lastname: Cammarata
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Novello
authors.forename: Daniela
authors.initials: D
authors.lastname: Galimberti
authors.forename: Elio
authors.initials: E
authors.lastname: Scarpini
authors.forename: Orazio
authors.initials: O
authors.lastname: Zanetti
authors.forename: Massimo
authors.initials: M
authors.lastname: Gennarelli
authors.forename: Massimo
authors.initials: M
authors.lastname: Tabaton
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D016022:Case-Control Studies; D060825:Cognitive Dysfunction / Q000235:genetics*; D015331:Cohort Studies; D005060:Europe; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D020932:Nerve Growth Factor / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011498:Protein Precursors / Q000235:genetics*
chemical_list: D011498:Protein Precursors; D020932:Nerve Growth Factor