Association study between P53 and P73 gene polymorphisms and the sporadic late-onset form of Alzheimer's disease.
An important pathological aspect of Alzheimer's disease (AD) is the apoptosis of neuronal and glial cells. Two members of the same protein family that regulates many genes involved in apoptosis are P53 and the heterologue P73. One single nucleotide polymorphism (SNP) in the gene encoding P53 (Arg72Pro, RS1042522), one dinucleotide polymorphism (G4C14-to-A4T14, RS 2273953, RS1801173) in the gene encoding P73, and two further SNPs in the same gene (-386 G/A, RS3765728; exon 5 T/C, RS1801174) were studied to determine whether DNA variations could influence the occurrence of the disease in a sample of Italian subjects with the sporadic late-onset form of AD. We observed that carrying the Pro/Pro genotype of P53 Arg72Pro was a risk factor with respect to the Pro/Arg + Arg/Arg genotypes [Odds Ratio (OR) = 2.02; 95% Confidence Interval (CI) 1.02-4.00; p = 0.047]. Furthermore, carrying the G/G genotype of the P73 -386 G/A was a risk factor with respect to the G/A + A/A genotypes (OR = 4.27; 95% CI 1.00-18.65; p = 0.047). A significant result was also obtained for P73 G4C14-to-A4T14. Among the patients, the homozygotes for the AT allele of this SNP had developed AD symptoms 5 years earlier than other genotypes (ANOVA p = 0.017). Though the results of particular polymorphisms analyses were not highly significant after correction for multiple comparisons, present data suggest that variation at the two genes may have a role in AD occurrence.
Scacchi
Renato
R
CNR Institute of Molecular Biology and Pathology, Department of Genetics and Molecular Biology, Sapienza University, Rome, Italy. Renato.Scacchi@uniroma1.it
Gambina
Giuseppe
G
Moretto
Giuseppe
G
Corbo
Rosa Maria
RM
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D000704:Analysis of Variance; D001057:Apolipoproteins E / Q000235:genetics; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012044:Regression Analysis; D018709:Statistics, Nonparametric; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D001057:Apolipoproteins E; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins