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J Am Coll Cardiol, 2000; 35:1192-1199
© 2000 by the American College of Cardiology Foundation
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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* {dagger}, Rolf Steffensen, MD{ddagger}, Gorm Jensen, MD, DMSc{dagger} and B.ørge G. Nordestgaard, MD, DMSc{dagger} §

* Department of Clinical Biochemistry, Herlev University Hospital, DK-2730, Herlev, Denmark
{dagger} The Copenhagen City Heart Study, Bispebjerg University Hospital, DK-2400 Copenhagen NV, Denmark
{ddagger} 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.

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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