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Cited by 77Lipoproteins and Cardiovascular HealthGenetic Associations and EpidemiologyParaoxonase enzyme and polymorphisms

Apolipoprotein E genotype: epsilon32 women are protected while epsilon43 and epsilon44 men are susceptible to ischemic heart disease

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Frikke-Schmidt, Ruth, Tybjærg-Hansen, Anne, Steffensen, Rolf, Jensen, Gorm, Nordestgaard, Børge G·2000·Journal of the American College of Cardiology
DOI 10.1016/s0735-1097(00)00520-9
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Abstract

Objectives We tested the hypothesis that risk of ischemic heart disease (IHD) differs as a function of apolipoprotein E (APOE) genotype in women and men. Background Apolipoprotein E genotype influences lipids and lipoproteins and, therefore, possibly the risk of IHD. Methods We genotyped 9,241 white women and men from the general population and 940 white women and men with IHD. Results Test of interaction suggested that APOE genotype may influence risk of IHD differently in women and men (p = 0.07). After age adjustment, the odds ratio (OR) for IHD for epsilon32 versus epsilon33 women was 0.57 (95% confidence interval [CI]: 0.35 to 0.94) while epsilon43 and epsilon44 versus epsilon33 men had ORs of 1.16 (0.96 to 1.41) and 1.58 (1.01 to 2.45). After adjustment for age and other conventional cardiovascular risk factors, the equivalent ORs were for epsilon32 women 0.38 (0.18 to 0.79), for epsilon43 men 1.35 (1.02-1.78) and for epsilon44 men 1.58 (0.80 to 3.08). Equivalent ORs for epsilon43 and epsilon44 versus epsilon33 women and for epsilon32 versus epsilon33 men were all close to 1.0 and nonsignificant. Of the total risk of IHD relative to the epsilon33 genotype, the fraction attributed to epsilon32 in women was -9%, while the fractions attributed to epsilon43 and epsilon44 in men were +8% and +2%. Conclusions Relative to epsilon33 individuals, epsilon32 women are protected while epsilon43 and epsilon44 men are particularly susceptible to IHD.

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  • Both APOE ε2 and ε4 alleles are associated with unfavourable lipid profiles.

    “Both ɛ2 and ɛ4 alleles are associated with unfavourable lipid profiles,12–19”

    From Plasma levels of apolipoprotein E, <i>APOE</i> genotype, and all-cause and cause-specific mortality in 105 949 individuals from a white general population cohort (2019) · cites this paper as [19]

    The ‘APOE genotype and lipids and lipoproteins’ section reports high triglycerides for ε22 and ε44, supporting an unfavourable association for some carriers of each allele. But the Discussion describes ε32 women as having lower cholesterol and apoB, higher HDL cholesterol, and an antiatherogenic lipoprotein profile. The claim therefore overgeneralizes the association for ε2. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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Authors
Frikke-Schmidt, R., Tybjærg-Hansen, A., Steffensen, R., Jensen, G., & Nordestgaard, B. G.
Affiliations
  • Copenhagen University Hospital (DK)
  • Bispebjerg Hospital (DK)
Corresponding author
Nordestgaard, Børge G
ORCID
Venue
Journal of the American College of Cardiology
Publisher
Elsevier BV
Published
2000-04
Volume
35
Issue
5
Pages
1192-1199
ISSN
0735-1097 (ISSN-L)
DOI
10.1016/s0735-1097(00)00520-9
OpenAlex
W147823787
Cited by
77
References
2
Citations by year
2025: 1 · 2024: 1 · 2023: 1 · 2022: 3 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 3 · 2015: 3 · 2014: 1 · 2013: 1 · 2012: 5
FWCI
7.39
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of the American College of Cardiology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
Keywords
APOE genotype, ischemic heart disease, sex differences, APOE ε4, APOE ε3, cardiovascular risk, genetic susceptibility, lipoproteins
MeSH terms
Adult, Aged, Aged, 80 and over, Apolipoproteins E, Denmark, Female, Genotype, Heterozygote, Humans, Male, Middle Aged, Polymorphism, Genetic, Risk Factors, Sex Characteristics, Case-Control Studies, Myocardial Ischemia, Sex Distribution, Genetic Predisposition to Disease, Apolipoprotein E3, Apolipoprotein E4, Apolipoprotein E2

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