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 higly significant after correction for multiple comparisons, present data suggest that variation at the two genes may have a role in AD occurrence.