GENETIC-MARKERS IN THE APO-AI-CIII-AIV GENE-CLUSTER FOR COMBINED HYPERLIPIDEMIA, HYPERTRIGLYCERIDEMIA, AND PREDISPOSITION TO ATHEROSCLEROSIS

The aim of the present study was to search for genetic determinants of combined hyperlipidemia and hypertriglyceridemia, and to evaluate whe ther such determinants might be associated with predisposition to athe rosclerosis. Four DNA polymorphisms in the apo AI-CIII-AIV gene cluste r (G to A mutation at position -75 basepairs in the apo Al promoter, X mnI, PstI and SstI) were studied in relation to combined hyperlipidemi a, hypertriglyceridemia, lipoprotein levels, atherosclerosis and age i n 221 Danish men. The frequency of the rare allele of the XmnI polymor phism, the X+ allele, was higher in individuals below 55 years of age with combined hyperlipidemia than in individuals with normal lipid lev els (0.31 vs. 0.14; P = 0.05). The rare allele of the SstI polymorphis m, the S+ allele, was more frequent in hypertriglyceridemic individual s compared with normotriglyceridemic individuals (0. 16 vs. 0.09; P < 0.05) and on analysis of variance the combined S-S+ and S+S+ genotypes were also associated with the highest triglyceride levels. Furthermor e, the frequency of the S+ allele decreased significantly as a functio n of age in nonatherosclerotic subjects (from 0.15 to 0.10 to 0.02 in 48-, 63- and 85-year-olds, respectively; 48- versus 85-year-olds, P = 0.03). These results suggest that genetic variation in the apo AI-CIII -AIV gene complex is associated with combined hyperlipidemia and hyper triglyceridemia and may have an impact on longevity and/or predisposit ion to atherosclerosis.