Alpha-1-antichymotrypsin (ACT or SERPINA3) polymorphism may affect age-at-onset and disease duration of Alzheimer's disease

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Kamboh M. I., Minster R. L., Kenney M., Ozturk A., Desai P. P., Kammerer C. M., ...Daha Fazla

NEUROBIOLOGY OF AGING, cilt.27, sa.10, ss.1435-1439, 2006 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 27 Sayı: 10
  • Basım Tarihi: 2006
  • Doi Numarası: 10.1016/j.neurobiolaging.2005.07.015
  • Dergi Adı: NEUROBIOLOGY OF AGING
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.1435-1439
  • Anahtar Kelimeler: ACT, genetic, association, Alzheimer's disease, CEREBROSPINAL-FLUID, ALPHA(1)-ANTICHYMOTRYPSIN, RISK, GENE, EXPRESSION, PROTEIN, PLASMA, ASSOCIATION, POPULATION, MODIFIER
  • Erciyes Üniversitesi Adresli: Hayır

Özet

In addition to genetic effects on disease risk, age-at-onset (AAO) of Alzheimer's disease (AD) is also genetically controlled. Using AAO as a covariate, a linkage signal for AD has been detected on chromosome 14q32 near the alpha 1-antichymotrypsin (ACT) gene. Previously, a signal peptide polymorphism (codon - 17A > T) in the ACT gene has been suggested to affect AD risk, but with inconsistent findings. Given that a linkage signal for AAO has been detected near ACT, we hypothesized that ACT genetic variation affects AAO rather than disease risk and this may explain the previous inconsistent findings between ACT genetic variation and AD risk. We examined the impact of the ACT signal peptide polymorphism on mean AAO in 909 AD cases. The ACT polymorphism was significantly associated with AAO and this effect was independent of the APOE polymorphism. Mean AAO among ACT/AA homozygotes was significantly lower than that in the combined AT + TT genotype group (p = 0.019) and this difference was confined to male AD patients (p = 0.002). Among male AD patients, the ACT/AA genotype was also associated with shorter disease duration before death as compared to the ACT/AT + TT genotypes (P = 0.012). These data suggest that the ACT gene may affect AAO and disease duration of AD. (c) 2005 Elsevier Inc. All rights reserved.