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Earlier onset of Alzheimer's disease: risk polymorphisms within PRNP, PRND, CYP46, and APOE genes.

J. Alzheimers Dis.2009;17(2):359-68
Ewa Golanska 1 , Krystyna Hulas-Bigoszewska , Monika Sieruta , Izabela Zawlik , Monika Witusik , Sylwia M Gresner , Tomasz Sobow , Maria Styczynska , Beata Peplonska , Maria Barcikowska , Pawel P Liberski , Elizabeth H Corder
Ewa Golanska 1 , Krystyna Hulas-Bigoszewska , Monika Sieruta , Izabela Zawlik , Monika Witusik , Sylwia M Gresner , Tomasz Sobow , Maria Styczynska , Beata Peplonska , Maria Barcikowska , Pawel P Liberski , Elizabeth H Corder
+ et al

[No authors listed]

Author information
  • 1 Department of Molecular Pathology and Neuropathology, Medical University of Lodz, Lodz, Poland. golanska@wp.pl

摘要


We studied eight polymorphisms within APOE, PRNP, PRND, and CYP46 genes in 213 Polish late-onset patients with Alzheimer's disease (AD) and 171 non-demented elderly controls. A latent classification approach, grade-of-membership analysis, was taken to identify three extreme pure type risk sets defined by the probabilities of being affected with AD and for genotypes found at the examined genes. Sets I and II represented high intrinsic risk, having a higher density of various genotypes compared to set III, at low intrinsic risk. A gradient of onset age depending on membership in the risk sets was also observed. Logistic regression analysis showed that the highest risk for AD was found for individuals who co-inherited APOE epsilon4 allele, PRNP codon 129 homozygosity, PRND codon 174 Thr allele, and CYP46 rs754203 g allele. AD can be influenced by genetic profiles leading to appearance of the disease, composed of genes which separately evoke a little or unnoticeable effect. Moreover, there may be multiple sufficient risk sets for AD. Looking at multiple genes together rather than analyzing them individually, may improve identification of risk alleles.