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

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 respectively). 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.

Apolipoprotein E genotype and plasma levels in coronary artery disease. A case-control study in the Italian population.

OBJECTIVES: To investigate the role of the apolipoprotein B and apolipoprotein E polymorphisms in coronary artery disease (CAD) susceptibility in the Italian population and their relation to plasma lipid and apolipoprotein levels. METHODS: APOB (APOB Xbal, EcoRI, Ins/Del), and APOE (APOE Cfol) polymorphisms were analyzed in 150 male CAD patients and 110 matched controls. In the same subjects plasma lipid, apoB, and apoE levels were measured. RESULTS: No differences in the distribution of the APOB polymorphisms were observed between patients and controls. Among patients the number of e*4-carriers was significantly higher than in controls. e*4-carriers were more frequent among the hypertensive patients and had a higher systolic blood pressure (p = 0.007) than the non-e*4 carriers. The APOB Xbal polymorphism was found to influence the distribution of HDL-cholesterol. Patients showed significantly lower levels of apoE (39.29 mg/L) than controls (54.32 mg/dL) and the lowest concentrations were associated to the E4/E3 and E4/E4 genotypes. CONCLUSION: Quantitative data are consistent with the hypothesis that apoE has an anti-atherosclerotic role and suggest that the apoE quantitation could be a useful parameter for defining cardiovascular risk. e*4 allele appears to be a risk factor for CAD in the Italian population and could act by its association with low apoE levels.

DNA polymorphisms of apolipoprotein B and angiotensin I-converting enzyme genes and relationships with lipid levels in Italian patients with vascular dementia or Alzheimer's disease.

The distribution of three DNA polymorphisms (XbaI, EcoRI, and I/D) of the apolipoprotein B (APOB) gene, and of the I/D polymorphism of the angiotensin I-converting enzyme (ACE) gene was investigated in 53 patients with vascular dementia, in 80 patients with late-onset sporadic Alzheimer's disease, and in 153 age-matched control subjects. Furthermore, plasma total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides were measured in the three groups and the involvement of the genetic variation at APOB locus on lipid levels was determined. Major findings of this work are (1) no genotype or allele of the polymorphisms examined here seemed to be associated with vascular dementia or with Alzheimer's disease, (2) total cholesterol and LDL cholesterol levels were lower in Alzheimer's disease patients than in vascular dementia patients and in elderly controls, and (3) the dementia patients with APOB EcoRI R+R- genotype had higher total cholesterol and LDL cholesterol levels than R+R+ homozygotes.

Apolipoproteins B and E, and angiotensin I-converting enzyme (ACE) genetic polymorphisms in Italian women with coronary artery disease (CAD) and their relationships with plasma lipid and apolipoprotein levels.

The XbaI, EcoRI and the signal peptide insertion/deletion (I/D) polymorphic sites of APOB gene, the CfoI polymorphic site of apolipoprotein E gene (APOE), and the insertion/deletion polymorphism of angiotensin I-converting enzyme (ACE) gene were studied using polymerase chain reaction (PCR) in 55 postmenopausal women with coronary artery disease (CAD) and in 119 control women of equivalent age. Patients and controls were recruited from the population of Rome, considered representative of Central and Southern Italy. There were no significant differences in allele frequencies between the two groups, though APOB X-, R- and I, APOE*3, and ACE D alleles were slightly more frequent in the cases than in the controls. The patients did not differ from the controls for plasma total cholesterol (TC), HDL-cholesterol, LDL-cholesterol, and apoAI values, while they presented significantly higher levels of triglycerides and apoB, and lower apoE levels. TC, apoE, and apoB quantitative values, adjusted for age, varied significantly among APOB XbaI and APOE genotypes. APOB X-X- genotype was associated in patients with a significantly lower mean TC concentration than the other two genotypes pooled together. APOE 3-2 genotype in the controls had significantly lower TC levels with respect to the other two pooled genotypic classes and higher apoE levels compared to 3-3 and 4-3 genotypes. In the patients, 3-2 genotype had significantly lower apoB levels than the pooled 3-3 and 4-3 class. We conclude that in the Italian women the DNA polymorphisms studied in this work do not seem to be important risk factors for CAD occurrence; that apoE quantitation could be another useful parameter to identify subjects at risk of CAD; and that APOB X- and APOE*2 are the alleles that most influence the interindividual plasma lipid variation among CAD female patients.

Apolipoprotein E (APOE) allele frequencies in late-onset sporadic Alzheimer's disease (AD), mixed dementia and vascular dementia: lack of association of epsilon 4 allele with AD in Italian octogenarian patients.

The Apolipoprotein E (APOE) epsilon 4 allele has been found to be strongly associated with Alzheimer's disease (AD) in most studies conducted up to now, though not all investigators have established a similar association with other forms of dementia, like vascular dementia. Our study examined the APOE polymorphism in a sample of 149 dementia patients, of which there were 80 with probable sporadic late-onset AD, 16 with a mixed form of dementia (MD), and 53 with vascular dementia (VD). An elderly control sample was composed of 126 subjects. The data obtained on the whole AD sample did not confirm the association already reported with APOE epsilon 4. A difference did emerge when the subjects were subdivided on the basis of age at the examination. AD patients aged < or = 80 years significantly differed from the correspondent elderly controls, while no difference was observed between the patients aged 81 years or older and controls. This pattern could be due to a previous disadvantageous effect of the epsilon 4 allele on the subjects bearing it. A substantially similar pattern was observed in the few MD patients, while no differences were found in the two VD subgroups. The odds ratio (OR) for AD associated with at least one epsilon 4 allele was significant and equal to 3.3 (95% CI = 1.2-9.1) for the < or = 80 age class, while it was not significant and equal to 1.1 (95% CI = 0.4-2.8) for the > 80 age class. Our data indicate that in AD patients aged less than 81 years, epsilon 4 is clearly associated with AD and that it can be considered a risk factor for AD chiefly before this age.