Influences of common variants of apolipoprotein E on measures of lipid metabolism in a sample selected for health.

Xhignesse, Marianne; Lussier‐Cacan, Suzanne; Sing, Charles F.; Kessling, Anna M.; Davignon, Jean

doi:10.1161/01.atv.11.4.1100

Cited by 119 publications

(67 citation statements)

References 27 publications

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“…Sing and Davignon [12] first published the observation that the presence of the e2 allele significantly reduced LDL cholesterol and the e4 allele increased it. This was later reported in several other studies [13][14][15][16][17] including an extensive analysis by Schaefer of a larger population stratified by sex and age [18]. There were no studies in Type 1 diabetics that investigated such a large population as that of the present study.…”

Section: Discussionsupporting

confidence: 67%

“…Given that one of the E2/2 subjects was hyperlipidemic (subject #4, Table 1), this subject's distribution is shown separately from the average of the five normolipidemic E2/2 subjects. Compared to the E3/3 subjects, the dyslipidemic E2/2 subject demonstrated an increase in VLDL (in fractions 28-37) particularly in the dense VLDL (VLDL remnants) (in fractions [31][32][33][34][35] and in IDL (in fractions [17][18][19][20][21][22][23][24][25][26][27][28][29][30]. In the absence of this dyslipidemic subject, the VLDL and IDL cholesterol distribution of the remaining normolipidemic E2/2 subjects were similar to, but appeared to be slightly higher, than that of the E3/3 subjects (Fig.…”

Section: Resultsmentioning

confidence: 93%

“…The fractions from the LDL and dense IDL density range were pooled into 3 groups corresponding to dense IDL/very buoyant LDL (pool 1, fractions [17][18][19][20], buoyant LDL (pool 2, fractions 13-16) and dense LDL (pool 3, fractions 9-12). The three pools were analyzed for lipid and apoprotein composition (Tables 2A and 2B).…”

Section: Resultsmentioning

confidence: 99%

“…The secondary goal of the study was to determine whether the apo E genotype affects LDL cholesterol mass and density distribution in this large population of Type 1 diabetics in a manner similar to that reported in several comprehensive studies of the non-diabetic population [12][13][14][15][16][17][18]. These studies have demonstrated that the e4 allele is associated with higher LDL cholesterol and the e2 allele with lower LDL cholesterol.…”

Section: Introductionmentioning

confidence: 95%

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LDL composition in E2/2 subjects and LDL distribution by Apo E genotype in type 1 diabetes

et al. 2007

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Apo E plays an important role in chylomicron and VLDL remnant processing, uptake or conversion to LDL. The type of lipoprotein that isolates in the LDL density of E2/2 subjects was investigated and the effect of the apo E isoforms on LDL mass was determined in all genotypes in a large group of Type 1 diabetics. Analysis of the LDL composition of E2/2 homozygotes (n = 6) compared to subjects with the common E3/3 isoform (n = 6) demonstrated an enrichment in apo E, unesterified cholesterol, phospholipid and triglyceride relative to apo B in E2/2 subjects, more typical of a dense IDL remnant than of LDL. Although diabetics were studied, these findings are considered to reflect those of the general population. Comparison of the lipoprotein distribution of homozygous and heterozygous subjects revealed that, as genotype changed from E4/4 (n = 22) to E3/4 (n = 262), E3/3 (n = 710) = E2/4 (n = 30), E2/3 (n = 151), E2/2 (n = 6), LDL cholesterol decreased significantly in a stepwise manner. The decrease was not in a specific subgroup of LDL. In conclusion, for E2/2 subjects, lipoproteins isolated in the LDL density range appear to be composed mainly of dense IDL remnants and some Lp(a). The apo E isoform also has a significant effect on LDL concentration in both homozygotes and heterozygotes.

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Section: Discussionsupporting

confidence: 67%

Section: Resultsmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

See 2 more Smart Citations

LDL composition in E2/2 subjects and LDL distribution by Apo E genotype in type 1 diabetes

et al. 2007

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“…This transformed variable (lnApoE) was used in this study to accommodate statistical tests that assume normality. We carried out separate analyses of females and males because of the well-documented gender-specific differences in the natural history of the risk of developing cardiovascular disease (Barrett-Connor, 1997;Hayward et al 2000;Matthews et al 1989;Thomas & Braus, 1998;Xhignesse et al 1991). To document such gender specificity in our study, we used Fisher's F-ratio to test whether there was a statistically significant difference in the phenotypic variance of age, height, weight, BMI or lnApoE between females and males (Sokal & Rohlf, 1995).…”

Section: Methodsmentioning

confidence: 99%

Evidence for Non‐additive Influence of Single Nucleotide Polymorphisms within the Apolipoprotein E Gene

Hamon

Stengård

Clark

et al. 2004

Annals of Human Genetics

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SummaryWe analyzed 13 single nucleotide polymorphisms (SNPs) within the apolipoprotein E (APOE) gene, to identify pairs of SNPs that interact in a non-additive manner to influence genotypic mean levels of the ApoE protein in blood. An overparameterized general linear model of two-SNP genotype means was applied to data from 456 female and 398 male unrelated European Americans from Rochester, MN, USA. We found statistically significant evidence for non-additivity between SNPs within the male sample, but not within the female sample. We observed nine pairs of SNPs with evidence of non-additivity at the α = 0.05 level of statistical significance within the male sample, when approximately three were expected by chance. Five of the nine pairs involved three SNPs (560, 624 and 1163) that did not have a statistically significant influence when considered separately in a single-site analysis. Three of the nine pairs involving four SNPs (832, 1998, 3937 and 4951) showed significant evidence for non-additivity in at least one of two other male samples from Jackson, MS, USA and North Karelia, Finland. Although all four of these SNPs had a statistically significant influence in Rochester when considered separately, only SNP 3937 gave a significant result in the other male samples. The four SNPs are located in the promoter, intronic and exonic regions, and 3' to the polyadenylation signal in the APOE gene. Our study suggests that analyses that only consider SNPs located in exons and ignore contexts such as those indexed by gender and population, and disregard non-additivity of SNP effects, may inappropriately model the contribution of a gene to the genetic architecture of a trait that has a complex multifactorial etiology.

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Apolipoprotein E allelic frequency in elderly smokers

Bowman

Brömeke

Lensing³

et al. 1998

Am. J. Med. Genet.

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Susceptibility genes for human diseases (e.g., cancer and atherosclerosis) increase disease risk by altering the metabolic activation of exogenous (e.g., carcinogens) and endogenous (e.g., cholesterol) compounds. The function of these genes, and subsequent risk, can be adversely affected by polymorphisms. This study tests the hypothesis that if specific genetic polymorphisms are related to mortality, then in elderly heavy smokers, there should be a decreased frequency of "at risk" alleles and an increased frequency of "protective" alleles, i.e., a survival effect. One such potential polymorphism is in the apolipoprotein E (apoE) gene, which is involved in cholesterol metabolism, where the epsilon4 allele is associated with an increased risk of coronary artery disease and is under represented in elderly populations. In this study, ApoE variant alleles were determined in 81 living, elderly current smokers (mean age: 72.5; range: 65-94; mean pack-years: 78; range: 13-192) and in 82 younger autopsy donors (mean age: 33; range: 1-58). There was a borderline difference in the apoE 4 allelic frequencies among the groups (11% in the elderly and 18% in the comparable younger group [df = 1; chi(2) = 4.02; P = 0.05]). A significant difference was found for age when stratified as a continuous variable by genotype in the elderly smokers (P = 0.03; mean age for persons with and without epsilon4 was 69.9 and 73.2, respectively). Pack-years of cigarette smokers did not differ by genotype, indicating no selective effect. These results confirm earlier associations for differences in the apoE allelic frequencies in the elderly and extend it to smokers, who generally have increased mortality at younger ages.

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Influences of common variants of apolipoprotein E on measures of lipid metabolism in a sample selected for health.

Cited by 119 publications

References 27 publications

LDL composition in E2/2 subjects and LDL distribution by Apo E genotype in type 1 diabetes

LDL composition in E2/2 subjects and LDL distribution by Apo E genotype in type 1 diabetes

Evidence for Non‐additive Influence of Single Nucleotide Polymorphisms within the Apolipoprotein E Gene

Apolipoprotein E allelic frequency in elderly smokers

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