EFFECTS OF GENDER AND MENOPAUSAL STATUS ON THE ASSOCIATION OF APOLIPOPROTEIN-E PHENOTYPE WITH PLASMA-LIPOPROTEIN LEVELS - RESULTS FROM THE FRAMINGHAM OFFSPRING STUDY
Ej. Schaefer et al., EFFECTS OF GENDER AND MENOPAUSAL STATUS ON THE ASSOCIATION OF APOLIPOPROTEIN-E PHENOTYPE WITH PLASMA-LIPOPROTEIN LEVELS - RESULTS FROM THE FRAMINGHAM OFFSPRING STUDY, Arteriosclerosis and thrombosis, 14(7), 1994, pp. 1105-1113
Apolipoprotein (ape)E phenotype is an important genetic determinant of
plasma low-density lipoprotein (LDL) cholesterol and apo B levels. We
have determined apo E phenotype by isoelectric focusing and plasma li
pid, lipoprotein cholesterol, apo A-I, apo B, and lipoprotein(a) level
s, as well as LDL particle size, in 2258 men and women participating i
n the Framingham Offspring Study. Apo E phenotype (E2/2, E2/4, E3/2, E
3/3, E3/4, and E4/4) was not associated with plasma lipoprotein(a) lev
els but was associated with plasma LDL cholesterol levels, apo B level
s, and LDL size in men and with plasma total cholesterol, LDL choleste
rol, and apo B levels in women. The average effect of the epsilon 2 al
lele was to lower plasma LDL cholesterol levels by 9.2 mg/dL in men an
d by 13.7 mg/dL in women, while the average effect of the epsilon 4 al
lele was to increase LDL cholesterol levels by 2.6 mg/dL in men and by
5.4 mg/dL in women. When men were divided into two groups according t
o their age (<50 and greater than or equal to 50 years old), the avera
ge effect of the epsilon 2 allele was to lower plasma levels of LDL ch
olesterol by 10.2 mg/dL in younger men and by 7.5 mg/dL in older men.
In premenopausal women, the average effect of the epsilon 2 allele was
to lower LDL cholesterol by 8.2 mg/dL and, in postmenopausal women, b
y 20.4 mg/dL. An opposite effect of the epsilon 4 allele was observed:
the epsilon 4 allele was associated with increases in plasma LDL chol
esterol levels of 4.0 mg/dL in younger men and of 1.0 mg/dL in older m
en. The epsilon 4 allele was associated with increases in plasma LDL c
holesterol levels of 1.6 mg/dL in premenopausal women and of 7.1 mg/dL
in postmenopausal women. The apo epsilon locus explained 1.0% of the
variance in LDL cholesterol levels in men and 2.1% in women. However,
only 0.5% of the LDL cholesterol level variance was due to variation a
t the epsilon locus in premenopausal women, whereas 5.0% of the LDL ch
olesterol level variance was explained by apo E polymorphism in postme
nopausal women. Our data indicate that the association of apo E phenot
ype with LDL cholesterol levels is significantly greater in postmenopa
usal women than in premenopausal women or in men.