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. © 2011 Elsevier B.V. and ECNP.
The CC genotype of transforming growth factor-β1 increases the risk of late-onset Alzheimer's disease and is associated with AD-related depression / Filippo, Caraci; Paolo, Bosco; Maria, Signorelli; Rosario S., Spada; Filomena I., Cosentino; Giuseppe, Toscano; Cinzia, Bonforte; Stefano, Muratore; Giuseppina, Prestianni; Simonetta, Panerai; Maria Concetta, Giambirtone; Eleonora, Gulotta; Carmelo, Romano; Maria Grazia, Salluzzo; Nicoletti, Ferdinando; Agata, Copani; Filippo, Drago; Eugenio, Aguglia; Raffaele, Ferri. - In: EUROPEAN NEUROPSYCHOPHARMACOLOGY. - ISSN 0924-977X. - 22:4(2012), pp. 281-289. [10.1016/j.euroneuro.2011.08.006]
The CC genotype of transforming growth factor-β1 increases the risk of late-onset Alzheimer's disease and is associated with AD-related depression
NICOLETTI, Ferdinando;
2012
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. © 2011 Elsevier B.V. and ECNP.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.