Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a group of 303 healthy Caucasian adults of both sexes we studied the influence of the apolipoprotein E (apo E) polymorphism on plasma levels of Lipoprotein(a) (Lp(a). The APOE*2 allele was found to decrease the mean plasma Lp(a) level by 24.8%, whereas the APOE*4 allele increased the mean Lp(a) level by 25.7%. These effects were parallel to the effect of apo E polymorphism on plasma cholesterol and low density lipoprotein (LDL)-cholesterol. For the Lp(a) levels, the genetic variance associated with the APOE locus contributed about 4% to the total phenotypic variance. For plasma cholesterol and LDL-cholesterol this contribution was 4.5 and 6.3%, respectively. We also found a significant positive correlation between LDL-cholesterol and Lp(a) levels. Since the apo E polymorphism effects LDL-receptor activity, we conclude that, at least in healthy normolipidemic individuals, plasma levels of Lp(a) are modulated by the LDL-receptor activity.
Atherosclerosis 1991 Oct
PMID:Apolipoprotein E polymorphism affects plasma levels of lipoprotein(a). 183 47

We have determined apolipoprotein E (apoE = protein, APOE = gene) polymorphism and its relationship with total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triglyceride levels in normoglycemic Hispanics (n = 446) and non-Hispanic whites (NHWs) (n = 659) as well as in diabetic Hispanics (n = 235) and NHWs (n = 116) from the San Luis Valley, Colorado. Effects were estimated separately for each group, and within each group men and women were analyzed separately; women were further categorized into pre- and post-menopausal status. The distribution of the APOE genotype pattern was comparable between the NHW normoglycemics and diabetics but it was significantly different among Hispanic normoglycemics and diabetics (P < 0.005). In the normoglycemic sample the APOE allele frequencies were significantly different between the two ethnic groups: the APOE*2 (0.09 vs. 0.05; P < 0.01) and APOE*4 (0.15 vs. 0.09; P < 0.002) allele frequencies were higher while the APOE*3 (0.76 vs. 0.86; P < 0.0001) allele frequency was lower in NHWs than in Hispanics. Significant variability among the three common APOE genotypes (3-2, 3-3, and 4-3) was observed for TC and LDL-C in normoglycemic Hispanic women (P = 0.09 and P = 0.03) but not in Hispanic men. In normoglycemic NHWs, however, significant mean differences among APOE genotypes were observed for TC and LDL-C in both women (P < 0.0001 and P < 0.0001) and men (P = 0.009 and P = 0.01). In Hispanic females, the APOE polymorphism accounted for 5.6% and 7.6% of the phenotypic variance for TC and LDL-C, respectively. In NHW females, the APOE polymorphism explained 10.2% of the phenotypic variance for TC and LDL-C, and in NHW males these values were 6.2% and 7.5%, respectively. There was no evidence of physiologic interaction between the APOE polymorphism and menopause status in affecting TC and LDL-C in NHW women (P = 0.65 and P = 0.55) but a suggestion of interaction was observed in Hispanic women for TC and LDL-C (P = 0.11 and 0.07). After the Hispanic women were stratified into pre- and postmenopausal groups, the effect of the APOE polymorphism on TC and LDL-C was significant only in the premenopausal group. Among diabetics, no significant effect of the APOE polymorphism was seen on cholesterol levels.(ABSTRACT TRUNCATED AT 400 WORDS)
Atherosclerosis 1995 Jan 20
PMID:The relationship of APOE polymorphism and cholesterol levels in normoglycemic and diabetic subjects in a biethnic population from the San Luis Valley, Colorado. 777 75

Consistent with previous reports, we observed a significant association of the APOE epsilon 4 allele with Alzheimer's Disease (AD) in a series of 91 autopsy-confirmed cases. The epsilon 4 allele frequency was higher in cases with a family history of AD-like dementia (0.54 +/- 0.07), although the epsilon 4 allele frequency in the AD cases with a negative family history (0.38 +/- 0.05) remained significantly greater than that for the non-AD control group (0.13 +/- 0.03). A similar increase in epsilon 4 allele frequency (0.54 +/- 0.07) was observed in the AD cases with amyloid angiopathy, compared to those who did not have amyloid angiopathy (0.36 +/- 0.04). Contrary to previous reports, no effect of the dosage of the epsilon 4 allele was found on the age of onset of dementia among the AD cases and, contrary to reports suggesting an association of epsilon 4 and atherosclerosis, the epsilon 4 allele frequency was similar in cases with or without concurrent brain infarcts. Modest but consistent correlations were observed between the dosage of epsilon 4 alleles and the cortical density of senile plaques, but not neurofibrillary tangles. The last finding suggests that the pathogenic events mediated by the epsilon 4 allele may be more directly involved in the formation of senile plaques, the identifying lesions in AD, than neurofibrillary tangles. A robust association of both the presence of an epsilon 4 allele and a family history of AD-like dementia with concurrent amyloid angiopathy occurred within our sample of AD cases. This association arose from an interaction of the epsilon 4 allele with a separate familial factor for which a family history of dementia served as a surrogate. These results suggest that amyloid angiopathy may be a common or central feature of a form of familial AD that is associated with the transmission of the APOE epsilon 4 allele.
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PMID:Association of the apolipoprotein E epsilon 4 allele with clinical subtypes of autopsy-confirmed Alzheimer's disease. 781 May 77

In an effort to dissect the genetic components of longevity, we have undertaken case-control studies of populations of centenarians (n = 338) and adults aged 20-70 years at several polymorphic candidate gene loci. Here we report results on two genes, chosen for their impact on cardiovascular risk, encoding apolipoprotein E (ApoE), angiotensin-converting enzyme (ACE). We find that the epsilon 4 allele of APOE, which promotes premature atherosclerosis, is significantly less frequent in centenarians than in controls (p < 0.001), while the frequency of the epsilon 2 allele, associated previously with type III and IV hyperlipidemia, is significantly increased (p < 0.01). A variant of ACE which predisposes to coronary heart disease is surprisingly more frequent in centenarians, with a significant increase of the homozygous genotype (p < 0.01). These associations provide examples of genetic influences on differential survival and may point to pleiotropic age-dependent effects on longevity.
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PMID:Genetic associations with human longevity at the APOE and ACE loci. 813 29

The distributions of plasma total cholesterol, apolipoproteins A-I and B and lipoprotein(a) levels as well as genetic typings of apolipoprotein(a) and apolipoprotein E were determined in a randomly selected sample of American Black women (mean age 22.2 +/- 6.5 years) . Mean plasma levels of cholesterol, apolipoprotein A-I, apolipoprotein B and lipoprotein(a) were 184.5 +/- 3.0 mg/dl, 138.0 +/- 3.1 mg/dl, 79.5 +/- 1.8 mg/dl and 24.5 +/- 1.5 mg/dl, respectively. Plasma lipoprotein (a) levels correlated significantly with apolipoprotein B and cholesterol. The contribution of apolipoprotein (a) and apolipoprotein E polymorphisms in affecting these quantitative traits was evaluated. The apolipoprotein(a) locus was extremely polymorphic with 27 alleles, while the 3 common alleles were observed in the apolipoprotein E gene. The frequencies of the APOE*2, APOE* and APOE*4 alleles were 0.094, 0.674 and 0.232, respectively. An inverse relationship was observed between the size of apolipoprotein(a) isoforms and lipoprotein(a) levels (r = 0.37; P = 0.0001). The apolipoprotein E polymorphism revealed a significant genotypic effect on apolipoprotein B (P = 0.0008) and cholesterol (P= 0.005) levels; these concentrations were lower in the APOE 2-3 genotype and higher in the 3-4 and 4-4 genotypes compared with the common 3-3 genotype. The apolipoprotein E polymorphism explained 15.8% and 6.3% of the phenotypic variance in apolipoprotein B and cholesterol levels, respectively. This study demonstrates that genetics play an important role in determining quantitative risk factors for coronary heart disease among American Black women.
Atherosclerosis 1995 Sep
PMID:Genetic effect of apolipoprotein(a) and apolipoprotein E polymorphisms on plasma quantitative risk factors for coronary heart disease in American black women. 854 57

The presence of apolipoprotein E-epsilon4 (APOE-epsilon4) allele has been implicated as a risk factor for Alzheimer's disease (AD). We examined the frequencies of APOE-epsilon4 alleles in age-matched controls and subgroups of 190 AD subjects exhibited cerebral amyloid angiopathy (CAA) and other frequently associated lesions. CAA was evident in 96% of the AD subjects, which were divided into two groups, one bearing mild or no apparent CAA and the other with moderate to severe CAA. APOE-epsilon4 allele frequency (48%) in the latter advanced CAA group was six times higher than in those who exhibited mild CAA. In the advanced CAA subjects, the occurrence of an epsilon4 allele was increased by a factor of 17 (95% confidence interval, 7.56 to 38.9). This was despite the fact that neocortical amyloid-beta plaque densities in the two groups were similar and that all of the AD subjects had met the accepted neuropathological criteria. We also observed that the degree of CAA severity was greatest in the group of subjects with the epsilon4/epsilon4 genotype. The association between CAA and APOE-epsilon4 was further implicated in two non-AD subjects among neurological controls with severe CAA. These two subjects, both homozygous for the APOE-epsilon4 allele, were primarily diagnosed as having Creutzfeldt-Jakob disease and Pick's disease in the absence of significant neocortical amyloid deposition. Allele frequency comparisons between neurological control subjects with CAA and those without likewise accorded a strong relationship between the APOE-epsilon4 allele and the presence of CAA. More remarkably, the epsilon4 allele frequency was highly associated with AD subjects exhibiting lobar or intracerebral hemorrhage, all of whom had advanced CAA. We observed that 36% of the AD subjects had concomitant cerebrovascular pathology resulting from single infarcts, multiple microinfarcts, ischemic white matter lesions, or petechial hemorrhages. Although the difference in APOE genotype distribution between subjects with and without cerebrovascular lesions did not reach statistical significance, we did note that the frequency of the epsilon4 allele was significantly higher in subjects with such pathology as compared with those without. However, we found no evidence to suggest that the acquisition of an APOE-epsilon4 allele or one of the alleles, epsilon2 or epsilon3, was a factor in the occurrence of atherosclerosis localized in the basal surface arteries. Analyses of our sample also confirm that there was a lower frequency of the APOE-epsilon2 allele in AD subjects and that the frequency of the epsilon4 allele in AD subjects with concomitant diffuse Lewy body disease was intermediate between controls and AD subjects. Our results suggest that the APOE-epsilon4 allele is a significant factor in the development of CAA in AD and reveal the possibility that APOE is an independent factor in CAA and other vascular abnormalities associated with AD.
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PMID:Apolipoprotein E-epsilon4 alleles in cerebral amyloid angiopathy and cerebrovascular pathology associated with Alzheimer's disease. 866 92

The Keewatin Inuit of the Northwest Territories of Canada have a very low age-adjusted mortality rate from coronary heart disease. We hypothesized that this apparent protection from disease has a genetic basis. We determined the prevalence of the disease-associated alleles of five candidate genes for atherosclerosis-related phenotypes. Surprisingly, four of the five alleles studied, namely AGT T235, FABP2 T54, PON R192 and APOE E4, were significantly more frequent in a sample of 175 Keewatin Inuit than among a representative control sample of whites living in the region. The high frequencies of these disease-associated alleles suggests either that they have no relationship with disease susceptibility in the Inuit, or that some unmeasured genetic and/or environmental factors mitigate disease susceptibility that is associated with these alleles. This highlights the difficulty in extrapolating findings from one population to another. Also, very modest genotype-phenotype associations were observed between APOE genotype (P = 0.016) and plasma low-density lipoprotein cholesterol concentration and between FABP2 genotype and plasma 2-h postprandial, glucose concentration (P = 0.048). The relationship between APOE alleles and plasma low-density lipoprotein cholesterol was the same as has been previously reported in many study samples. However, the relationship between FABP2 alleles and plasma 2-h postprandial glucose concentrations was the opposite to that reported in other studies. This suggests that differences in environment, such as the type of fatty acid consumed, interacts with functional differences in gene products involved in candidate metabolic pathways to produce phenotypic differences.
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PMID:Are Canadian Inuit at increased genetic risk for coronary heart disease? 918 78

A 49 year-old hypercholesterolemic male with marked electrocardiographic ST segment depression on exercise testing was found to have an apo E E3/3 phenotype by isoelectric focusing, but an APOE E4/3 genotype using HhaI restriction isotyping. DNA sequence analysis of the proband's APOE gene found a G-->C point mutation at codon 251. This predicted a change in the amino acid encoded by codon 251, from arginine to glycine. The mutation occurred on an allele that encoded arginine at position 112 and this variant was named APOE R112; R251G. The R251G change altered a recognition site for the endonuclease StuI and was the basis for a restriction isotyping method to rapidly screen for this mutation. In relatives of the proband, APOE R112; R251G was consistently found in subjects with both hyperlipidemia and atherosclerosis. Apo E R112; R251G-containing very low density lipoproteins bound normally to macrophages in vitro. However, the proband had an abnormal post-prandial lipoprotein response to a dietary fat challenge. The association of APOE R112; R251G with abnormal phenotypes suggests that the amino acid change in the carboxy-terminal, perhaps in combination with the common amino acid polymorphism at codon 112, has a functional impact upon lipoprotein metabolism in members of this family.
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PMID:Apolipoprotein E R112; R251G: a carboxy-terminal variant found in patients with hyperlipidemia and coronary heart disease. 936 Jun 38

The APOE gene is located on chromosome 19, and the three common alleles are designated epsilon2, epsilon3, and epsilon4. The epsilon4 allele is associated with increased plasma cholesterol, atherosclerosis and cardiovascular disease, Alzheimer's disease, and decreased longevity. The objective of the present study was to estimate the distribution of APOE alleles in the Greek population by DNA analysis. The material consisted of 216 voluntary, healthy Greek blood donors (146 males/70 females). The APOE allele frequencies were epsilon2: 5.3%, epsilon3: 88.2%, epsilon4: 6.5%. The epsilon4 allele frequency of 6.5% in the Greek population is, together with the frequency in the Chinese population, among the lowest in the world.
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PMID:Apolipoprotein E polymorphism in the Greek population. 938 26

Transgenic technologies have provided a series of very useful mouse models to study hyperlipidemia and atherosclerosis. Normally, mice carry cholesterol mainly in the high density lipoprotein (HDL) sized lipoproteins, and have low density lipoprotein (LDL) and very low density lipoprotein (VLDL) cholesterol levels. These low LDL and VLDL levels are due to the very rapid metabolism of remnant clearance in mice, which hamper metabolic studies. In addition, due to the lack of atherogenic lipoproteins, mice will not readily develop atherosclerosis. This situation has changed completely, because to date, most known genes in lipoprotein metabolism have been used in transgenesis to obtain mice in which genes have been silenced or overexpressed. These experiments have yielded many mouse strains with high plasma lipid levels and a greater susceptibility for developing atherosclerosis. One of the most widely used strains are knock-out mice deficient for apoE, which is one of the central players in VLDL metabolism. Subsequently, a wide variety of other transgenic studies involving APOE have been performed elucidating the role of apoE and apoE mutants in lipolysis, remnant clearance, cellular cholesterol efflux and atherogenesis. In addition, the APOE mouse models are excellent tools for the development of gene therapy for hyperlipidemias.
Atherosclerosis 1998 Mar
PMID:Transgenic mouse models to study the role of APOE in hyperlipidemia and atherosclerosis. 956 31


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