+10 T/C polymorphisms in the gene of transforming growth factor-beta1 are associated with neurodegeneration and its clinical evolution.
Transforming growth factor-beta1 (TGF-beta1) acts as an immunosuppressant by inhibiting the expression of several pro-inflammatory cytokines. Its gene contains single nucleotide polymorphisms (SNPs) at codon +10 (T-->C) and +25 (G-->C) that appear to influence the level of expression of TGF-beta1. We investigated these SNPs in 198 healthy controls (HC), 193 patients with Alzheimer's disease (AD) and 48 patients with mild cognitive impairment (MCI). Among the latter, after a 4-year follow-up, 21 were diagnosed as AD (MCI-->AD) while 18 did not progress (stable MCI). We observed that both the +10 C allele and the CC genotype were over-represented in AD when compared to HC. These variants significantly raised the risk of disease independently of the status of apolipoprotein E4. The CC genotype was also over-expressed in MCI, especially in MCI-->AD. These results suggest that TGF-beta1 may be one of the early markers involved in the inflammatory mechanisms underlying the pathogenesis of AD.
Arosio
Beatrice
B
Geriatric Unit, Ospedale Maggiore Policlinico, IRCCS, University of Milan, Italy. beatrice.arosio@unimi.it
Bergamaschini
Luigi
L
Galimberti
Lorenza
L
La Porta
Caterina
C
Zanetti
Mariella
M
Calabresi
Carmen
C
Scarpini
E
E
Annoni
Giorgio
G
Vergani
Carlo
C
D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D019636:Neurodegenerative Diseases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
D053773:Transforming Growth Factor beta1