Earlier onset of Alzheimer's disease: risk polymorphisms within PRNP, PRND, CYP46, and APOE genes.
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.
Department of Molecular Pathology and Neuropathology, Medical University of Lodz, Lodz, Poland. golanska@wp.pl
Ewa
E
Golanska
Krystyna
K
Hulas-Bigoszewska
Monika
M
Sieruta
Izabela
I
Zawlik
Monika
M
Witusik
Sylwia M
SM
Gresner
Tomasz
T
Sobow
Maria
M
Styczynska
Beata
B
Peplonska
Maria
M
Barcikowska
Pawel P
PP
Liberski
Elizabeth H
EH
Corder
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics*; D016009:Chi-Square Distribution; D000072556:Cholesterol 24-Hydroxylase; D005260:Female; D058851:GPI-Linked Proteins; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics*; D012307:Risk Factors; D013250:Steroid Hydroxylases / Q000235:genetics*
D001057:Apolipoproteins E; D058851:GPI-Linked Proteins; C501125:PRND protein, human; C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions; D013250:Steroid Hydroxylases; D000072556:Cholesterol 24-Hydroxylase