Effects of apolipoprotein A-IV genotype on glucose and plasma lipoprotein levels.

The effects of apolipoprotein (apo) A-IV genotype on serum glucose, total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, triglyceride and glucose concentrations were ascertained in a population of 373 men and 361 women with a mean age of about 57 years. Subjects were evaluated at entry into a lifestyle intervention program. Apolipoprotein A-IV genotype variations at residues 347 and 360 were examined, as these mutations affect the sequence of apo A-IV, a major protein constituent of intestinal triglyceride-rich lipoprotein and HDL. With regard to the apo A-IV 360 mutation, 16.4% of the females and 13.4% of the males carried the apo A-IV 2-allele, almost entirely in the heterozygous state. No effect of the apo A-IV 1/2 genotype was observed in either men or women on total cholesterol, LDL cholesterol, HDL cholesterol, triglyceride, the total cholesterol (TC)/HDL ratio, or on A-I, A-IV and apo B levels. This was also the case for the apo A-IV 347 mutation. However, women with the apo A-IV 360 1/2 genotype had significantly (p < 0.005) higher glucose levels (105.5 mg/dl) compared with the 1/1 wild-type (94.0 mg/dl). All analyses were also adjusted for age, body mass index, medications, alcohol use and cigarette smoking. The prevalence of the 347 mutation was somewhat higher than the 360 mutation, with 29% of the females and 32.0% of the males being heterozygous for this mutation, and 3.9% of the females and 5.4% of the males being homozygous for this mutation. These data are consistent with the concept that the apo A-IV 360 and 347 genotypes have no significant effect on apo A-IV levels and other lipid parameters in either gender. However, apo A-IV 360 1/2 genotype did have a significant effect on serum glucose levels in women.

Effects of apolipoprotein A-I genetic variations on plasma apolipoprotein, serum lipoprotein and glucose levels.

The present authors investigated the individual and combined associations of the apolipoprotein (apo) A-I -75 bp and +83 bp polymorphisms with plasma lipid, lipoprotein and apolipoprotein levels in 734 Caucasian men and women. The frequency of the A allele at position -75 bp (G-->A) was 0.14 in women and 0.17 in men. The frequencies for the rare M2 allele at position +83 bp and/or 84 bp (C-->T and G-->A, respectively) were 0.04 and 0.05 in women and men, respectively. In women, the A allele was associated with significantly higher levels of apo B (P = 0.016), total cholesterol (TC) (P = 0.005), low-density lipoprotein cholesterol (LDL-C) (P = 0.018) and TC:high-density lipoprotein (HDL) ratio (P = 0.026) compared to the G/G subjects. In men, no significant associations were detected between the -75 bp polymorphism and any lipid trait examined. The M2 allele for the +83 bp polymorphism was significantly associated in men with higher levels of apo A-I (P = 0.002) and TC (P = 0.046). In women, a significant effect was observed for TC (P = 0.036), with M2+/- subjects having lower levels than M2+/+ subjects. Significant linkage disequilibrium (P = 0.037) between the apo A-I -75 bp and +83 bp polymorphisms was detected. Women carrying both rare alleles (G/A M2+/-) had significantly higher TC:HDL ratios (P = 0.031) compared to the other haplotypes. In men, significant differences were observed for apo A-I (P = 0.021) and TC (P = 0.044), with carriers of the G/G M2+/- haplotype having the highest values compared to other genotype combinations. In conclusion, the -75 bp (G/A) polymorphism appears to have a significant effect on levels of apo B, plasma TC and LDL-C in women, while the +83 bp polymorphism seems to affect the apo A-I levels in men, and the plasma cholesterol levels in both genders.

Effects of age, gender, and lifestyle factors on plasma apolipoprotein A-IV concentrations.

Apolipoprotein (apo) A-IV is a protein component of triglyceride (TG)-rich lipoproteins and high density lipoproteins (HDL). Plasma apo A-IV levels were measured by immunoelectrophoresis and these values were related to other biological variables in 723 middle aged and elderly men and women (more than 90% of them were Caucasian) prior to participation in a lifestyle modification program. Apo A-IV may play an important function in regulating lipid absorption, reverse cholesterol transport, and food intake. The data are consistent with the following concepts: (1) apo A-IV levels are significantly and positively correlated with age (r = 0.159, P < 0.05) in all subjects, with plasma apo A-I levels in both men (r = 0.194, P < 0.001) and women (r = 0.213, P < 0.001), and with apo E (r=0.111, P<0.05) and TG levels (r =0.120, P <0.05) in men; (2) apo A-IV levels are inversely correlated with body mass index (r = 0.170, P <0.05) in women; (3) female subjects on hormone replacement therapy have significantly lower plasma apo A-IV levels (by 4.1%, P < 0.05) than normal controls; (4) diabetic subjects have significantly higher apo A-IV levels (by 21%, P < 0.01) than normal subjects; (5) there is no significant effect of smoking, alcohol intake, and apo A-IV-1/2 genotype on apo A-IV levels. The data indicate that plasma apo A-IV levels are significantly affected by age, diabetes, and hormone replacement therapy.

Association of apolipoprotein (Apo)E genotype with plasma apo E levels.

The purpose of this study was to investigate the effects of apolipoprotein (apo) E genotype on plasma apo E levels as well as serum total, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride, and glucose values in 734 middle-aged and elderly, female and male subjects. Apo E allele frequencies were similar to those reported in other Caucasian populations. After adjustment for medications, alcohol use, smoking, age, and body mass index, apo E genotype was noted to have significant effects on apo E, total cholesterol, LDL cholesterol, and glucose levels in females, and on apo E, LDL cholesterol, and HDL cholesterol levels, as well as the total cholesterol (TC)/HDL cholesterol ratio in males. Female and male subjects with the apo E4 allele had significantly (P<0.05) lower plasma apo E (25 and 15%) and higher LDL cholesterol levels (5 and 2%), while those with the apo E2 allele had significantly (P<0.05) higher apo E (32 and 27%) and lower LDL cholesterol levels (10 and 10%) than the apo E3/3 group. Moreover, female apo E4 carriers had significantly (P<0.05) lower glucose values (11%) than the apo E3/3 group. These data are consistent with the concept that, in addition to the well known effects of apo E genotype on LDL-C values, this locus plays a very significant role in modulating plasma apo E levels.