title: The CC genotype of transforming growth factor-β1 increases the risk of late-onset Alzheimer's disease and is associated with AD-related depression.
abstract: Transforming growth factor-β1 (TGF-β1) is a neurotrophic factor that exerts neuroprotective effects against β-amyloid-induced neurodegeneration. Recently, a specific impairment of the TGF-β1 signaling pathway has been demonstrated in Alzheimer's disease (AD) brain. TGF-β1 is also involved in the pathogenesis of depressive disorders, which may occur in 30-40% of AD patients. The TGF-β1 gene contains single nucleotide polymorphisms (SNPs) at codon +10 (T/C) and +25 (G/C), which are known to influence the level of expression of TGF-β1. We investigated TGF-β1 +10 (T/C) and +25 (G/C) SNPs and allele frequencies in 131 sporadic AD patients and in 135 healthy age- and sex-matched controls. Genotypes of the TGF-β1 SNPs at codon +10 (T/C) and +25 (G/C) did not differ between AD patients and controls, whereas the allele frequencies of codon +10 polymorphism showed a significant difference (P = 0.0306). We also found a different distribution of the +10 (C/C) phenotype (continuity-corrected χ(2) test with one degree of freedom = 4.460, P = 0.0347) between late onset AD (LOAD) patients and controls (P = 0.0126), but not between early onset AD (EOAD) patients and controls. In addition, the presence of the C/C genotype increased the risk of LOAD regardless of the status of apolipoprotein E4 (odds ratio [OR] = 2.34; 95% CI = 1.19-4.59). Compared to patients bearing the T/T and C/T polymorphisms, LOAD TGF-β1 C/C carriers also showed > 5-fold risk to develop depressive symptoms independently of a history of depression (OR = 5.50; 95% CI = 1.33-22.69). An association was also found between the TGF-β1 C/C genotype and the severity of depressive symptoms (HAM-D(17) ≥ 14) (P < 0.05). These results suggest that the CC genotype of the TGF-β1 gene increases the risk to develop LOAD and is also associated with depressive symptoms in AD.
authors.affiliation: Department of Drug Sciences, University of Catania, Catania, Italy. carafil@hotmail.com
authors.forename: Filippo
authors.initials: F
authors.lastname: Caraci
authors.forename: Paolo
authors.initials: P
authors.lastname: Bosco
authors.forename: Maria
authors.initials: M
authors.lastname: Signorelli
authors.forename: Rosario S
authors.initials: RS
authors.lastname: Spada
authors.forename: Filomena I
authors.initials: FI
authors.lastname: Cosentino
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Toscano
authors.forename: Cinzia
authors.initials: C
authors.lastname: Bonforte
authors.forename: Stefano
authors.initials: S
authors.lastname: Muratore
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Prestianni
authors.forename: Simonetta
authors.initials: S
authors.lastname: Panerai
authors.forename: Maria Concetta
authors.initials: MC
authors.lastname: Giambirtone
authors.forename: Eleonora
authors.initials: E
authors.lastname: Gulotta
authors.forename: Carmelo
authors.initials: C
authors.lastname: Romano
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Salluzzo
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Nicoletti
authors.forename: Agata
authors.initials: A
authors.lastname: Copani
authors.forename: Filippo
authors.initials: F
authors.lastname: Drago
authors.forename: Eugenio
authors.initials: E
authors.lastname: Aguglia
authors.forename: Raffaele
authors.initials: R
authors.lastname: Ferri
mesh_terms: D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics* / Q000523:psychology; D053327:Apolipoprotein E4 / Q000097:blood; D016022:Case-Control Studies; D003863:Depression / Q000150:complications / Q000235:genetics* / Q000523:psychology; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics* / Q000523:psychology; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
chemical_list: D053327:Apolipoprotein E4; D053773:Transforming Growth Factor beta1