APOLIPOPROTEIN-B GENE POLYMORPHISMS IN ISCHEMIC-HEART-DISEASE AND HYPERCHOLESTEROLEMIA - EFFECTS OF AGE AND SEX

The association of polymorphic alleles of the apolipoprotein B gene (I nsertion/Deletion-, XbaI-, MspI-, EcoRI-, and 3'-VNTR polymorphisms) w ith variation in lipid concentrations (total cholesterol (T-C), HDL ch olesterol (HDL-C), and log-triglycerides (TG)) in plasma was studied i n 259 men and 59 women with moderate hypercholesterolemia (T-C 5.5-8.0 mmol/l and TG<2.5 mmol/1) and ischemic heart disease, especially in r elation to the effect of sex and age. The XbaI and the Ins/Del polymor phic alleles were associated with variation in T-C, but only in patien ts below the 75th percentile for age. The XbaI and Ins/Del polymorphic alleles were synergistically associated with variation in T-C: the X and the Del alleles were associated with higher cholesterol concentra tions. Younger male patients had the highest frequency of haplotypes i ncluding both the X+ and the Del alleles, but the most striking differ ence was a significantly higher frequency of haplotypes including both the X- and the Ins alleles in female and in older male patients. The heterogeneity of association of polymorphic alleles in the apolipoprot ein B gene to complex traits like hypercholesterolemia and ischemic he art disease in this study could explain why in most studies the X+ all ele has been associated with higher cholesterol levels, whereas the X- allele has been associated with symptomatic atherosclerosis. The resu lts of our study emphasize the importance of age and sex in measured g enotype association studies.