Showing papers by "Rosa Maria Corbo published in 2001"

Polymorphisms in the apolipoprotein E gene regulatory region in relation to coronary heart disease and their effect on plasma apolipoprotein E.

Abstract: In a previous study which examined the distribution of apolipoprotein E genotypes and plasma levels in a sample of male coronary heart disease (CHD) patients and controls, we found a significant excess of the genotypes carrying APOE * 4 allele in CHD men (18.2%) vs. controls (9.6%) and an association between the APOE * 4 allele and the lowest concentrations of apoE. In the present investigation, we re-examined in the same samples two recently identified polymorphisms in the promoter region of APOE, -491A/T and -427T/C, which may alter the level of apoE expression. No differences in the distributions of the -491A/T genotypes and alleles were observed between cases and controls (-491 * A = 0.760 and 0.757 respectivelyl. Polymorphism -427T/C showed in CHD patients an excess of -427 * C allele (patients vs. controls = 0.123 vs. 0.074) and corresponding genotypes that was marginally significant. Stratification of the samples according to the presence/absence of APOE * 4 showed that the excess of the -427 * C allele concerned only CHD patients not carrying APOE * 4 allele (patients vs. controls = 0.133 vs. 0.061; p=0.017). This result suggests that the presence of -427 * C allele could represent a risk for developing CHD in subjects with E2/E2, E3/E2, and E3/E3 genotypes. Studies carried out on patients with Alzheimer's disease demonstrated that -491A/T and -427T/C polymorphisms affect the level of plasma apoE. In the present study, carried out on CHD patients and controls, the genetic variation at -427 and -491 sites of the APOE regulatory region had no apparent effect on apoE plasma concentration.

Polymorphisms of the Apolipoprotein E Gene Regulatory Region and of the LDL Receptor Gene in Late-Onset Alzheimer’s Disease in Relation to the Plasma Lipidic Pattern

Abstract: Two new polymorphisms in the regulatory region of the apolipoprotein E gene, –491 A/T and –427 T/C, have been reported to be associated with the risk of Alzheimer’s disease (AD). Moreover, in vitro studies suggest that the two polymorphisms modulate the levels of apoE protein expression. We examined these two polymorphisms, as well as the MspI polymorphism in the LDL receptor gene, in a series of elderly patients with late-onset sporadic AD and in an age-matched control group but failed to find any kind of association between these genetic features and an increased risk of AD. In the same samples we investigated the relationships between various genotypes and plasma lipid levels. Since the well-known effect of the three-allelic APOE polymorphism on plasma lipid levels could mask the effect of other polymorphisms, the analyses were performed taking into account the APOE genotype. The two regulatory region polymorphisms had significant effects only on the apoE levels. The –427 TT homozygotes had lower, and the –491 AA homozygotes had higher levels of apoE than other genotypes. This result confirmed in vivo the already observed in vitro effects of –491 A/T and –427 T/C polymorphisms on APOE promoter transcription activity.