ARTICLE
Apolipoprotein E genotype: epsilon32 women are protected while epsilon43 and epsilon44 men are susceptible to ischemic heart disease
The Copenhagen City Heart Study
Ruth Frikke-Schmidt, MD*,
Anne Tybjærg-Hansen, MD, DMSc*  ,
Rolf Steffensen, MD ,
Gorm Jensen, MD, DMSc and
B.ørge G. Nordestgaard, MD, DMSc 
* Department of Clinical Biochemistry, Herlev University Hospital, DK-2730, Herlev, Denmark
The Copenhagen City Heart Study, Bispebjerg University Hospital, DK-2400 Copenhagen NV, Denmark
Department of Medicine B, Division of Cardiology, Rigshospitalet, Copenhagen University Hospital, DK-2100 Copenhagen Ø, Denmark
Department of Clinical Biochemistry, Glostrup University Hospital, DK-2600, Glostrup, Denmark
Manuscript received June 29, 1999;
revised manuscript received October 27, 1999,
accepted December 15, 1999.
Reprint requests and correspondence: Dr. Børge G. Nordestgaard, Department of Clinical Biochemistry, Herlev University Hospital, DK-2730 Herlev, Denmark
brno{at}herlevhosp.kbhamt.dk
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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Abbreviations and Acronyms
| | APOE | = apolipoprotein E | | bp | = base pair | | CI | = confidence interval | | HDL | = high density lipoprotein | | HRT | = hormonal replacement therapy | | IHD | = ischemic heart disease | | LDL | = low density lipoprotein | | OR | = odds ratio | | PCR | = polymerase chain reaction |
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