Apolipoprotein E genotype and cardiovascular disease in the Framingham Heart Study.
BACKGROUND
Apolipoprotein (apo) E is a constituent of lipoproteins with considerable variation due to cysteine-arginine exchanges. The apo E4 (Arg112-Cys) polymorphism has been associated with dementia and hypercholesterolemia. We investigated the relation of APOE genotype to cardiovascular disease (CVD) in the Framingham Offspring Study.


RESULTS
DNA was isolated from 3413 study participants and APOE genotypes were determined utilizing the polymerase chain reaction and restriction isotyping. In the entire group of subjects, 20.7% had apo E4/4 or E3/4 (Group E4); 14.1% had apo E2/2 or E2/3 (Group E2) and 63.9% had the apo E3/3 genotype (Group E3). Subjects with E2/4 (1.3%) were excluded. Period prevalence of CVD between examinations 1 and 5 (1971-1994) (366 events) was related to APOE genotype. Age adjusted period prevalence of CVD in men was 18.6% for Group E4, 18.2% for Group E2 and 12.7% for Group E3 (P=0.004); while in women these rates were 9.9, 4.9, and 6.6%, respectively (P=0.037). After adjustment for non-lipid risk factors the relative odds for CVD in Group E2 men was 1.79 (P=0.0098) and in Group E4 it was 1.63 (P=0.0086) compared with the Group E3; while in Group E4 women it was 1.56 (P=0.054). After adjustment for all CVD risk factors, the relative odds in Group E2 men was 1.94 (P=0.004) and in Group E4 men it was 1.51 (P=0.0262).


CONCLUSIONS
The presence of the apo E2 or apo E4 alleles in men is associated with significantly greater CVD risk. This genotypic information may help to identify individuals at increased risk for CVD events.
Lipid Metabolism Laboratory, Jean Mayer-USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington St, Boston, MA 02111, USA.
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C
Lahoz
E J
EJ
Schaefer
L A
LA
Cupples
P W
PW
Wilson
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Levy
D
D
Osgood
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Parpos
J
J
Pedro-Botet
J A
JA
Daly
J M
JM
Ordovas
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D053329:Apolipoprotein E2; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000235:genetics*; D002648:Child; D015331:Cohort Studies; D003327:Coronary Disease / Q000453:epidemiology / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008404:Massachusetts; D008875:Middle Aged; D016017:Odds Ratio; D015995:Prevalence; D017678:Sex Distribution
D053329:Apolipoprotein E2; D053327:Apolipoprotein E4; D001057:Apolipoproteins E