VARIABILITY GENE EFFECTS OF DNA POLYMORPHISMS AT THE APO-B, APO-A-I C-III AND APO-E LOCI ON SERUM-LIPIDS - THE CARDIOVASCULAR RISK IN YOUNGFINNS STUDY/

We studied the influence of selected genetic markers on the intra-indi vidual long-term variability in serum lipid levels. The study cohort c onsisted of a sub-sample from a large follow-up study of atheroscleros is precursors in children and young adults. A total of 320 subjects ha d determinations of apo B XbaI RFLP genotypes, 305 subjects had ape AI /CIII SstI RFLP genotype determinations and 1581 subjects had their ap o E phenotypes determined. Complete data on serum lipids were availabl e at 3-year intervals over a 6-year follow-up period. The subjects wer e healthy and aged 3-18 years at baseline. Intra-individual variabilit y was assessed with a nested analysis of variance procedure. Each of t he genetic markers studied here significantly affected intra-individua l variability of serum lipid levels. No clear sex influence was observ ed, although the differences in variability tended to be more signific ant in males. Apo B XbaI genotypes significantly influenced intra-indi vidual variability of total and LDL-cholesterol levels in both sexes. A marked effect of the XbaI genotype was also found on triglyceride va riability. In males the standardized intra-individual triglyceride var iances were 0.71 and 0.34 in genotypes X1X1 and X2X2, respectively (p< 0.001), with a clear gene dosage effect. The apo AI/CIII genotype had an influence only on the variability of total cholesterol and LDL-chol esterol levels and only in males. The apo E phenotypes were associated with intra-individual variability in total and LDL-cholesterol levels but again, only in males. The lowest variability was observed in the phenotype E4/3 where high mean values were also observed. We also exam ined the effect of combined genetic markers. Up to 7 times greater var iability was found in the combination E3/2+S1S1 compared to combinatio n E4/3 + S1S2 (p < 0.001). In addition, mean levels of, e.g., LDL-chol esterol were 70% greater in the combination of E4/3 + S1S2 compared to E3/2+S1S1. This implies that subjects with both these genetic markers have high LDL-cholesterol values that also tend to remain constantly elevated. In conclusion, it is evident that many of the presently know n DNA polymorphisms of the coronary heart disease candidate gene loci also influence intraindividual variability of serum lipid or lipoprote in levels. These findings can be used to further refine our ability to predict the risk of a cardiovascular event.