DNA POLYMORPHISMS OF THE APOPROTEIN-B-GENE ARE ASSOCIATED WITH ALTERED PLASMA-LIPOPROTEIN CONCENTRATIONS BUT NOT WITH PERCEIVED RISK OF CARDIOVASCULAR-DISEASE - EUROPEAN ATHEROSCLEROSIS RESEARCH STUDY

Three polymorphisms of the apoprotein B gene (XbaI, signal peptide ins ertion/deletion and the 3'-variable number of tandem repeats) selected on the basis of previously published reports as likely to be the most informative, were investigated in a cross-cultural study in Europe, S tudents from 14 universities, grouped for analyses into five regions, were recruited as cases (n = 682) if they had a paternal history of pr emature myocardial infarction. For comparison, twice the number of age - and sex-matched controls (n = 1312) were recruited from the same stu dent populations. There were significant regional differences in allel e frequencies of the XbaI and VNTR polymorphisms but not of the signal peptide. There were no significant differences in allele frequencies between cases and controls. Adjusted for age, gender and region, the l ipoprotein concentrations differed significantly with genotype. The Xb aI polymorphism was associated with differences in plasma cholesterol (P = 0.007), triglyceride (P = 0.050), apo B (P = 0.001) and LDL chole sterol (P = 0.01). An interaction between XbaI genotype and body mass index was observed on plasma triglyceride (P = 0.015) and apo B (P = 0 .005) concentrations. The signal peptide deletion allele was associate d with increased plasma cholesterol (P = 0.03), apo B (P = 0.04) and L DL cholesterol (P = 0.02). The VNTR was not significantly associated w ith any of these variables although there was a significant genotype/s tatus interaction in relation to HDL cholesterol (P = 0.001) and apo A I (P = 0.001) concentrations. We conclude that, although they are asso ciated with significant differences in lipoprotein concentrations with in- and between-populations, the apo B DNA polymorphisms studied are o f less value as indicators of cardiovascular risk-factor status in the offspring of individuals affected by the disease.