Several sequence variations were examined for being endogenous "risk markers" in the development of CHD. The "markers" in this study included: the PstI-SstI RFLPs in the apo AI-CIII gene cluster, the EcoRI-MspI RFLPs in the apo B100 gene and the SstI RFLP in the 5' flanking region of the insulin gene. The study population comprised 700 individuals of German origin. A strong association of these "markers" to the disease phenotype predicts their loss in healthy individuals with ages above that of the prevalent incidence of CHD. In contrast, these "markers" should accumulate in diseased persons. A significant age-dependent selection was observed for the EcoRI RFLP in the apo B100 gene. This was the case when the allele and genotype frequencies of healthy old individuals were compared with those of newborns. In contrast, no RFLP showed significant differences in allele and genotype distributions between patients defined by coronary angiography and controls. In the group of patients, but not controls, several RFLP genotypes were found to be associated with significantly higher serum levels of cholesterol and triglycerides. This was true in the case of serum cholesterol comparing the genotypes S1S2 with those of S1S1 (p = 0.05) observed for the SstI polymorphic site in the 3' noncoding region of the apo CIII gene. Significantly higher levels of triglycerides were found within the heterozygous patients P1P2 (p = 0.045) and S1S2 (p = 0.02) than in the homozygotes P1P1 and S1S1 for the PstI-SstI RFLPs at the apo AI-CIII gene cluster.(ABSTRACT TRUNCATED AT 250 WORDS)