No abstract

An association between the 19q13.2 chromosomal region and Alzheimer's disease (AD) has been reported in AD families and for sporadic AD. Recent observations provide evidence that the epsilon 4 allele of the apolipoprotein E gene (APOE), located in this region, is a risk factor for late-onset AD. Within this region, other genes possibly involved in the pathophysiology of AD and in strong linkage disequilibrium with the APOE locus may be responsible for this association. To test this hypothesis, we analysed the allelic distribution of four polymorphic genetic markers flanking the APOE gene (D19S178 (CA)n repeat, D19S47 (CA)n repeat, APOCI HpaI restriction fragment length polymorphism, APOCII (CA)n repeat). We performed these analyses in a sample of late-onset sporadic cases (n = 36) versus controls (n = 38), and in a sample of early-onset sporadic cases (n = 34) versus controls (n = 36). Early-onset cases were analysed for two cut-offs with late-onset: less than 60 and less than 65. We observed a significant increased frequency of the APOE epsilon 4 allele in late-onset and early-onset AD with ages at onset less than 60 and less than 65. The adjusted odds ratio (OR) of the bearers of at least one APOE epsilon 4 allele was 4.10 ([1.84;9.16]) when estimated in both populations with a logistic regression model. Surprisingly, the odds ratio of the bearers of at least one APOE epsilon 2 allele was also significant and equal to 0.11 ([0.02;0.50]) suggesting a possible protective effect.(ABSTRACT TRUNCATED AT 250 WORDS)

No abstract

Apolipoprotein E (APOE) is a major protein in lipid metabolism existing in three common isoforms: APOE2, -3 and -4. The varepsilon4 allele of the APOE gene ( APOE ) coding for the APOE4 isoform is associated with an increased risk of myocardial infarction (MI) and of Alzheimer's disease (AD). Recently, several polymorphisms in the APOE regulatory region have been reported. Some of these have been associated with AD and modified APOE allelic mRNA expression in AD brains. Here, we have investigated whether three of these promoter polymorphisms (-491AT, -427CT and -219GT) can also modify cardiovascular risk. The hypothesis was tested in a large multicentre case-control study of MI, the ECTIM Study, on 567 cases and 678 controls. Among the three APOE promoter polymorphisms tested, only the-219T allele was associated with a significantly increased risk of MI (OR = 1.29, 95% CI: 1.09-1.52, P < 0.003) and the effect was shown to be independent of the presence of the other mutations, including the APOE epsilon2/epsilon3/epsilon4 polymorphism. Moreover, the-219T allele greatly decreased the APOE plasma concentrations in a dose-dependent manner ( P < 0.008). These data indicate that the-219GT polymorphism of the APOE regulatory region emerges as a new genetic susceptibility risk factor for MI and constitutes another common risk factor for both neurodegenerative and cardiovascular diseases.