title: Association of a polymorphism of the transforming growth factor-beta1 gene with cerebral amyloid angiopathy.
abstract: 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.
authors.affiliation: Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa 920-8640, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hamaguchi
authors.forename: S
authors.initials: S
authors.lastname: Okino
authors.forename: N
authors.initials: N
authors.lastname: Sodeyama
authors.forename: Y
authors.initials: Y
authors.lastname: Itoh
authors.forename: A
authors.initials: A
authors.lastname: Takahashi
authors.forename: E
authors.initials: E
authors.lastname: Otomo
authors.forename: M
authors.initials: M
authors.lastname: Matsushita
authors.forename: H
authors.initials: H
authors.lastname: Mizusawa
authors.forename: M
authors.initials: M
authors.lastname: Yamada
mesh_terms: 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
chemical_list: 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