Genetic variation in the apolipoprotein AI-CIII-AIV gene cluster and coronary heart disease.

Six RFLPs in the apolipoprotein (apo) AI-CIII-AIV gene region detected with the restriction enzymes XmnI, MspI, PstI, SstI and PvuII were used to study the role of genetic variation at this locus in the development of coronary heart disease and in the regulation of serum levels of various lipid and lipoprotein parameters in the Austrian population. 106 male patients with coronary heart disease and 118 matched controls were investigated. None of the alleles defined by these RFLPs was associated with increased coronary risk. In the patients, but not in the control group individuals with the genotype P1P2 for the PstI polymorphism in the 3' flanking region of the apo AI gene had significantly lower serum levels of high density lipoprotein (HDL)-cholesterol and apo AI levels than those with the genotype P1P1. The S2 allele of the SstI polymorphism at the 3' end of the apo CIII gene was significantly associated with elevated serum levels of triglycerides in the patient, but not in the control group. Controls with the genotype V2V2 for the PvuII(A) polymorphism at the 5' end of the apo CIII gene had significantly higher serum levels of apo B than those with V1V1 or V1V2. This association did not exist among the patients. These findings suggest that variation associated with some of these RFLPs is contributing to the determination of lipid levels in patients and controls, but that the RFLPs themselves cannot be used as markers for increased coronary risk in the Austrian population.