| Effects of apolipoprotein and low density lipoprotein receptor gene polymorphisms on lipid metabolism, and the lipid risk factors of coronary artery disease | ||
|---|---|---|
| Prev | Chapter 6. Discussion | Next |
The various apo B polymorphisms and apo E phenotypes were not related to the slow clearance of autologous LDL, and, overall, no major differences between autologous and homologous LDL were observed among the study patients.
Three patients cleared homologous LDL markedly (9.0-19.3 %) faster than their own LDL, but this difference was considerably smaller than in the patients with FDB, who clear autologous LDL at a 48% slower rate than homologous LDL (Vega & Grundy 1986, Innerarity et al. 1990). Neither the apo B-3500 nor the apo-B-3531 mutation was detected in our patients, and this study confirms the earlier findings that FDB is not a common cause of hypercholesterolemia in Finland (Hämäläinen et al. 1990).
Our study confirms the earlier associations between the presence of the XbaI cutting site and elevated cholesterol values, and part of the effect might be due to the slightly lower LDL catabolic rate in the individuals with the XbaI cutting site. It has been demonstrated earlier that the XbaI polymorphism modifies dietary fat and cholesterol responses in such a way that individuals having the XbaI cutting site are more responsive to a low-fat, low-cholesterol diet that those lacking the cutting site (Tikkanen et al. 1992). This could, in part, explain the differences in the lipoprotein composition associated with the XbaI polymorphism. Patients treated with the prostaglandin E analogue RS-86505-007 who were homozygous for the presence of the XbaI restriction site of the apolipoprotein B gene tended to have smaller reductions in total and LDL cholesterol, although the concentrations before the drug treatment were similar. However, the response to the drug is different from the dietary effect, hypercholesterolemic patients homozygous for the restriction site being more resistant to the drug. The difference in response could be due to different sites of action. Medication interfering with fat and cholesterol absorption may alter the formation of lipoprotein particles in the intestine, whereas the interaction between the apo B polymorphism and the diet most probably occurs at the level of the removal of LDL particles from the circulation.
An association between elevated triglycerides and the absence of the EcoRI cutting site has been reported in coronary heart disease patients (Paulweber et al. 1990, Tybjaerg-Hansen et al. 1991) and in healthy males (Paulweber et al. 1990). In our population, individuals homozygous for the EcoRI restriction site had slow LDL catabolic rates associated with high LDL and total cholesterol values. We suggest that the polymorphism could have an effect on cholesterol metabolism, at least in hypercholesterolemic individuals.
The MspI polymorphism has not been associated with variations in serum lipid concentrations (Hegele et al. 1986, Xu et al. 1989, Genest et al. 1990). Our results confirm these findings.
We were unable to confirm any of the lipid associations reported earlier and found no differences in the concentration or production of apo B, which suggests that the polymorphism is not associated with changes in the processing or post-translational modification of apo B that would affect the catabolism of LDL.