| Effects of apolipoprotein and low density lipoprotein receptor gene polymorphisms on lipid metabolism, and the lipid risk factors of coronary artery disease | ||
|---|---|---|
| Prev | Chapter 5. Results | Next |
Neither the apo B-3500 mutation nor the apo B-3531 mutation were detected in this population.
The effects of the XbaI polymorphism of apolipoprotein B on the lipid values, lipoprotein composition, LDL apo B contents and production, and autologous and homologous FCR are shown in Table 5-2. The XbaI genotype -/- was associated with lower plasma levels of total, IDL and LDL cholesterol compared to the other genotypes, the differences being statistically significant between the homozygous XbaI -/- and the heterozygous XbaI +/- genotypes. Also, the chemical composition of the apo B containing lipoprotein particles was associated with XbaI RFLP. The protein-cholesterol ratio was high and the cholesterol-triglyceride ratio low in XbaI -/- homozygotes, and their apo B concentration was also low. There was a tendency towards higher autologous LDL FCR in the patients with XbaI -/- compared with the other genotypes.
Table 5-2. Lipid values, lipoprotein composition, and LDL apoB metabolism by XbaI genotype.
| XbaI -/- | XbaI +/- | XbaI +/+ | p | ||
|---|---|---|---|---|---|
| Male/Female | 10/4 | 17/12 | 2/4 | ||
| BMI (kg/m2) | 25.6 (3.0) | 27.5 (3.5) | 26.7 (3.6) | 0.51 | |
| Cholesterol (mmol/l) | |||||
| Tot | 7.03* (0.82) | 8.11* (1.09) | 7.96 (0.85) | 0.006 | |
| VLDL | 1.08 (0.75) | 1.37(0.84) | 0.84 (0.33) | 0.23 | |
| IDL | 0.37*(0.18) | 0.65*(0.4635) | 0.39 (0.13) | 0.01 | |
| LDL | 4.35* (0.68) | 5.05* (0.92) | 5.29 (0.74) | 0.02 | |
| HDL | 1.37 (0.40) | 1.16 (0.30) | 1.43 (0.32) | 0.07 | |
| Triglycerides (mmol/l) | |||||
| tot | 1.98 (1.06) | 2.25 (1.17) | 1.62 (0.50) | 0.36 | |
| VLDL | 1.08 (0.73) | 1.20 (0.82) | 0.75 (0.40) | 0.42 | |
| IDL | 0.12 (0.04) | 0.15(0.08) | 0.11 (0.03) | 0.21 | |
| LDL | 0.37 (0.09) | 0.49 (0.19) | 0.36 (0.07) | 0.04 | |
| Prot/chol | |||||
| VLDL | 0.81(0.21) | 0.68 (0.16) | 0.70 (0.10) | 0.08 | |
| IDL | 0.66 (0.15)* | 0.53 (0.16)* | 0.56 (0.14) | 0.04 | |
| LDL | 0.65 (0.11) | 0.70 (0.12) | 0.60 (0.06) | 0.10 | |
| HDL | 3.39 (0.73) | 3.79 (0.79) | 3.23 (0.40) | 0.14 | |
| Chol/trigly | |||||
| VLDL | 0.30 (0.05) | 0.36 (0.10) | 0.37(0.08) | 0.06 | |
| IDL | 1.38 (0.43)* | 1.93 (0.73)* | 1.51(0.34) | 0.02 | |
| LDL | 5.44 (1.74) | 5.04 (1.91) | 6.49 (0.98) | 0.20 | |
| Lipoprotein (a)x (mg/dl) | 24 (2-85) | 14 (0.5-143) | 28 (2-87) | 0.54 | |
| LDL apoB (mg/dl) | 111* (19) | 146* (28) | 121 (12) | 0.002 | |
| LDL apo B production (mg/kg/day) | 15.1 (4.5) | 16.5 (3.9) | 13.9 (2.3) | 0.26 | |
| LDL apoB FCR (pool/day) | 0.30 (0.05) | 0.28 (0.06) | 0.28 (0.02) | 0.57 | |
| x median and range. Triglyceride and Lp(a) comparisons are non-parametric (Kruskal-Wallis). * difference between the groups is statistically significant. FCR=fractional catabolic rate. | |||||
The EcoRI genotype +/+ was associated with higher total, VLDL and LDL cholesterol than the genotypes +/- and -/-, but the differences were not statistically significant. The chemical composition of the lipoprotein particles was quite similar in the genotype groups, the only difference being the higher cholesterol-triglyceride ratio in the subjects with the EcoRI +/+ genotype. The autologous FCR of LDL apo B was significantly lower in the subjects with the EcoRI +/+ genotype compared to EcoRI +/-, 0.27 (0.05) and 0.31 (0.06) pools/day, respectively.
The MspI and ins/del polymorphisms were not associated with variations in the lipid or apo B concentrations, lipoprotein particle composition or catabolism of LDL apo B.
The influence of the apolipoprotein B gene XbaI and EcoRI polymorphisms on the lipid-lowering capacity of RS-86505-007 was studied in patients receiving the drug 6 mg tid. Patients homozygous for the XbaI restriction site tended to have smaller reductions in total and LDL cholesterol than those who had only one or no allele with the cutting site, although the differences were not statistically significant. No differences were detected in the lipid changes of patients with or without the EcoRI restriction site.