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 insertion/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. Students from 14 universities, grouped for analyses into five regions, were recruited as cases (n = 682) if they had a paternal history of premature myocardial infarction. For comparison, twice the number of age- and sex-matched controls (n = 1312) were recruited from the same student populations. There were significant regional differences in allele 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 lipoprotein concentrations differed significantly with genotype. The XbaI polymorphism was associated with differences in plasma cholesterol (P = 0.007), triglyceride (P = 0.050), apo B (P = 0.001) and LDL cholesterol (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 associated with increased plasma cholesterol (P = 0.03), apo B (P = 0.04) and LDL cholesterol (P = 0.02). The VNTR was not significantly associated with any of these variables although there was a significant genotype/status interaction in relation to HDL cholesterol (P = 0.001) and apo AI (P = 0.001) concentrations. We conclude that, although they are associated with significant differences in lipoprotein concentrations within- and between-populations, the apo B DNA polymorphisms studied are of less value as indicators of cardiovascular risk-factor status in the offspring of individuals affected by the disease.
Turner
P R
PR
Facultat de Medicina, Universitat Rovira i Virgili, Reus, Spain.
Talmud
P J
PJ
Visvikis
S
S
Ehnholm
C
C
Tiret
L
L
D000293:Adolescent; D000328:Adult; D000483:Alleles; D001055:Apolipoproteins B / Q000235:genetics*; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics*; D003431:Cross-Cultural Comparison; D004247:DNA / Q000235:genetics*; D005060:Europe; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008074:Lipoproteins / Q000097:blood*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012107:Research Design; D012307:Risk Factors
D001055:Apolipoproteins B; D008074:Lipoproteins; D004247:DNA