Association of a polymorphism of the transforming growth factor-beta1 gene with cerebral amyloid angiopathy.
BACKGROUND
A recent study showed that transforming growth factor-beta1 (TGF-beta1) induces amyloid-beta deposition in cerebral blood vessels and meninges of a transgenic mouse model of Alzheimer's disease (AD), and that TGF-beta1 mRNA levels are correlated with cerebral amyloid angiopathy (CAA) in human AD brains. A T/C polymorphism at codon 10 in exon 1 of the TGF-beta1 gene has been reported to be associated with the serum TGF-beta1 concentration. We investigated whether the TGF-beta1 polymorphism is associated with the risk of CAA.


METHODS
The association between the severity of CAA and the T/C polymorphism at codon 10 in exon 1 of the TGF-beta1 was investigated in 167 elderly Japanese autopsy cases, including 73 patients with AD. The apolipoprotein E (APOE) genotype was also determined.


RESULTS
The genotypes (TT/ TC/ CC) were associated with the severity of CAA significantly in all patients (p = 0.0026), in non-AD patients (p = 0.011), and APOE non-epsilon4 carriers (p = 0.0099), but not in AD patients or APOE epsilon4 carriers. The number of the T alleles positively correlated with the severity of CAA in all patients (p = 0.0011), non-AD patients (p = 0.0026), and APOE non-epsilon4 carriers (p = 0.0028), but not in AD patients or APOE epsilon4 carriers. The polymorphism was not significantly associated with AD.


CONCLUSIONS
Our results suggest that the polymorphism in TGF-beta1 is associated with the severity of CAA, especially in non-AD patients and APOE non-epsilon4 carriers.
Hamaguchi
T
T
Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa 920-8640, Japan.
Okino
S
S
Sodeyama
N
N
Itoh
Y
Y
Takahashi
A
A
Otomo
E
E
Matsushita
M
M
Mizusawa
H
H
Yamada
M
M
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000208:ethnology / Q000235:genetics / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D016657:Cerebral Amyloid Angiopathy / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D003062:Codon / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012720:Severity of Illness Index; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D003062:Codon; D012333:RNA, Messenger; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1