Table 3 Baseline values and lipid changes adjusted for sex and age by apo E
genotypes
o 3 o3 n = 132
o 3 o4 n = 29
o 2 o3 n = 25
Total cholesterol Baseline
234.87 9 39.15 212.78 9 32.52
a
204.48 9 39.68 11.42 9 21.60
Change 7.28 9 26.60
10.06 9 26.15 LDL cholesterol
Baseline 194.21 9 42.42
169.02 9 32.72
a
159.14 9 42.58 10.97 9 23.48
Change 8.52 9 26.80
9.93 9 21.31 HDL cholesterol
Baseline 35.72 9 6.10
37.35 9 7.63 39.61 9 8.96
− 0.16 9 6.24
1.09 9 7.71 Change
1.68 9 5.63 Triglyceride
Baseline 171.83 9 89.37
149.22 9 90.01 142.38 9 72.78
Change −
4.16 9 46.82 5.95 9 55.68
− 11.30 9 45.89
a
P50.01. Table 5
Baseline values and lipid changes adjusted for sex and age by CETP I405 polymorphic site
V¯V n = 34 V¯I n = 88
I¯I n = 72 Total cholesterol
219.23 9 39.61 Baseline
216.15 9 30.41 212.86 9 38.35
10.48 9 26.01 Change
11.02 9 20.99 10.88 9 23.02
LDL cholesterol 176.45 9 37.64
Baseline 172.06 9 33.26
170.00 9 40.06 Change
9.28 9 25.95 10.30 9 21.11
10.08 9 21.69 HDL cholesterol
38.08 9 8.30 36.76 9 7.26
36.99 9 6.64 Baseline
Change 0.34 9 4.73
1.33 9 6.43 2.02 9 5.93
Triglyceride 158.14 9 88.34
152.68 9 89.13 146.83 9 85.07
Baseline Change
4.48 9 51.41 −
1.27 9 53.37 4.00 9 54.02
were performed on sex and age adjusted values. Our results from the crossover study indicate an overall
significant effect of the diets on plasma cholesterol, LDL-C and triglyceride concentrations data not
shown. For all variables, no carry over effect was demonstrated, and the order of the given diets had no
effect on the response of the lipid phenotypes. Due to these results, the mean values of the two determinations
made at the end of the LSC diet compared with that determined at the end of the HSC diet, irrespective of
the order of the diets, were used in order to test the null hypothesis that phenotypic change was not associated
with the genetic variation at the gene locus under study Tables 2 – 5.
The frequency of apoB polymorphisms is similar to those previously described in the Israeli population
[14,35]. The frequency distribution of apoE genotype treatment and period in this basic two-period crossover
design were assessed by means of t-tests according to Fleiss [46]. Analysis of variance was performed in order
to examine the homogeneity of baseline levels and changes across the genotype groups.
5. Results
Study participants comprised 108 males and 106 females. The mean of age was 46.4 years range 15 – 74
for men and 44.0 years range 14 – 70 for women. The means of BMI were 26.0 9 3.1 and 25.7 9 4.2 for
men and women, respectively. Since the variability of the change in lipids and lipoproteins was found to be
associated with age and not with BMI, further analyses
Table 4 Baseline values and lipid changes adjusted for sex and age by LPL polymorphic sites
S447stop N291S
T-93G N¯S n = 4
N¯N n = 190 T¯T n = 185
S¯stop n = 45 S¯S n = 146
T¯G n = 9 Total cholesterol
207.68 9 30.59 220.72 9 49.46
Baseline 216.80 9 36.55
215.36 9 34.90 209.40 9 29.37
215.84 9 35.32 13.63 9 21.17
Change 10.71 9 22.78
18.44 9 21.36 9.73 9 22.41
13.75 9 23.52 10.73 9 22.85
LDL cholesterol 171.66 9 36.45
190.24 9 43.04 173.26 9 38.25
Baseline 166.30 9 30.09
165.69 9 34.65 172.35 9 36.72
9.77 9 21.93 11.12 9 15.40
Change 9.99 9 22.41
11.53 9 24.31 9.25 9 21.27
27.06 9 30.78 HDL cholesterol
37.49 9 6.94 37.61 9 7.58
b
Baseline 27.56 9 2.67
37.25 9 7.38 37.91 9 8.70
37.40 9 7.69 1.52 9 5.92
a
− 3.57 9 7.67
1.08 9 5.72 2.52 9 6.68
Change 1.33 9 5.93
3.16 9 6.98 Triglyceride
134.32 9 78.09 151.79 9 87.33
120.38 9 60.66 159.58 9 91.18
b
220.14 9 147.12 149.53 9 85.15
a
Baseline 0.67 9 50.87
b
50.51 9 122.16 2.16 9 56.86
0.53 9 39.20 3.07 9 51.97
a
− 26.51 9 69.98
Change
a
0.05BP50.1.
b
P50.05.
was in Hardy – Weinberg equilibrium and in a relatively uniform pattern allele frequencies: o2 = 0.079, o3 =
0.815, o4 = 0.105 similar to that previously described in other populations [47]. All the LPL and CETP
polymorphisms
were also
in Hardy – Weinberg
equilibrium. Table 2 presents the average lipid and lipoprotein
levels at baseline and the average changes from the end of LSC diet to the end of the HSC diet for the different
apo B genotypes. Subjects homozygous for the apo B XbaI restriction site allele designated as + + showed
a smaller change in plasma cholesterol 1.1 mgdl and LDL-C 0.3 mgdl levels compared to subjects with the
X-allele 11.4 mgdl and LDL-C 10.6 mgdl. How- ever, these differences in change between the two XbaI
genotype groups were not statistically significant for total cholesterol P = 0.092 and for LDL-C P =
0.098. Subjects heterozygous for the less frequent apo B EcoRI allele GL4145 showed a significant change
in plasma cholesterol 16.2 mgdl and LDL-C 15.6 mgdl levels, compared with a smaller change for
cholesterol 8.0 mgdl and LDL-C 6.2 mgdl among subjects homozygous for the apoB EcoRI restriction
site allele GG4154. These differences in change be- tween the EcoRI genotype groups were statistically
significant P = 0.01 for total cholesterol and P = 0.007 for LDL-C. The Apo B signal peptide polymorphism
appeared to influence the response of HDL-C to the intervention diet. HDL-C change among the SP2724
insertiondeletion alleles heterozygotes was greater than that observed in the SP2727 genotype; however,
this difference was not significant P = 0.099.
Table 3 indicates that although TC and LDL-C baseline levels were significantly different among the
apo-E genotypes, there were no significant apo E geno- type effects on lipid and lipoprotein changes.
Mean TG and HDL-C on the basal diet and the average response to diet were significantly different
among LPL genotypes Table 4. Triglyceride baseline values were higher P = 0.092 and HDL-C significantly
lower P = 0.008 among subjects found to be het- erozygous for the LPL N291S mutation. A heteroge-
neous
response for
HDL-C was
observed for
individuals harboring the S291 allele compared to those homozygous for the N291 allele. Baseline triglyceride
levels were also found to be significantly affected by the LPL S447stop mutation. Finally, we observed a statisti-
cally non-significant P = 0.1 influence of the LPL-93 mutation on the triglyceride response to the dietary
change; Triglyceride declined among the TG het- erozygotes compared to a slight increase among those
individuals with the TT genotype.
In the present study, there were no significant effects of the CETP genotypes on lipid and lipoprotein base-
line levels and on their response to dietary manipula- tions Table 5.
6. Discussion
