title: IGF-I gene variability is associated with an increased risk for AD.
abstract: Insulin-like growth factor I (IGF-I), a neuroprotective factor with a wide spectrum of actions in the adult brain, is involved in the pathogenesis of Alzheimer's disease (AD). Circulating levels of IGF-I change in AD patients and are implicated in the clearance of brain amyloid beta (Aβ) complexes. To investigate this hypothesis, we screened the IGF-I gene for various well known single nucleotide polymorphisms (SNPs) covering % of the gene variability in a population of 2352 individuals. Genetic analysis indicated different distribution of genotypes of 1 single nucleotide polymorphism, and 1 extended haplotype in the AD population compared with healthy control subjects. In particular, the frequency of rs972936 GG genotype was significantly greater in AD patients than in control subjects (63% vs. 55%). The rs972936 GG genotype was associated with an increased risk for disease, independently of apolipoprotein E genotype, and with enhanced circulating levels of IGF-I. These findings suggest that polymorphisms within the IGF-I gene could infer greater risk for AD through their effect on IGF-I levels, and confirm the physiological role IGF-I in the pathogenesis of AD.
authors.affiliation: Neuroscience Laboratory, Research Center, Hospital 12 de Octubre, Madrid, Spain.
authors.forename: Teo
authors.initials: T
authors.lastname: Vargas
authors.forename: Ana
authors.initials: A
authors.lastname: Martinez-Garcia
authors.forename: Desiree
authors.initials: D
authors.lastname: Antequera
authors.forename: Elisabet
authors.initials: E
authors.lastname: Vilella
authors.forename: Jordi
authors.initials: J
authors.lastname: Clarimon
authors.forename: Ignacio
authors.initials: I
authors.lastname: Mateo
authors.forename: Pascual
authors.initials: P
authors.lastname: Sanchez-Juan
authors.forename: Eloy
authors.initials: E
authors.lastname: Rodriguez-Rodriguez
authors.forename: Ana
authors.initials: A
authors.lastname: Frank
authors.forename: Marcel
authors.initials: M
authors.lastname: Rosich-Estrago
authors.forename: Alberto
authors.initials: A
authors.lastname: Lleo
authors.forename: Laura
authors.initials: L
authors.lastname: Molina-Porcel
authors.forename: Rafael
authors.initials: R
authors.lastname: Blesa
authors.forename: Teresa
authors.initials: T
authors.lastname: Gomez-Isla
authors.forename: Onofre
authors.initials: O
authors.lastname: Combarros
authors.forename: Felix
authors.initials: F
authors.lastname: Bermejo-Pareja
authors.forename: Fernando
authors.initials: F
authors.lastname: Valdivieso
authors.forename: Maria Jesus
authors.initials: MJ
authors.lastname: Bullido
authors.forename: Eva
authors.initials: E
authors.lastname: Carro
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000453:epidemiology* / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D018260:Gelsolin / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011228:Prealbumin / Q000235:genetics; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology; D018709:Statistics, Nonparametric
chemical_list: D001057:Apolipoproteins E; D018260:Gelsolin; D011228:Prealbumin; D007334:Insulin-Like Growth Factor I