ABSTRACT
Apolipoprotein B XbaI polymorphism and apolipoprotein AI/CIII SstI polymorphism have been found to be associated with variations in serum lipoprotein levels. We investigated whether these gene polymorphisms are involved in determining the lipid-modulating action of gemfibrozil. Of the 221 male subjects with hyperlipidemia studied, 121 responded well to the treatment with more than a 25% reduction in the non-high-density lipoprotein cholesterol level, whereas 100 were nonresponders. Among responders, but not nonresponders, homozygosity for the apolipoprotein B X2 allele (XbaI site present) and heterozygosity for the apolipoprotein AI/CIII S2 allele (SstI site present) were associated with elevated baseline serum low-density lipoprotein cholesterol and triglyceride levels, respectively. However, the hypolipidemic effect of gemfibrozil among the responders was independent of these gene polymorphisms. These data indicate that common polymorphisms of the apolipoprotein B and apolipoprotein AI/CIII gene loci influence serum lipid levels by mechanisms that are amenable to an intervention with gemfibrozil.
Subject(s)
Apolipoproteins A/genetics , Apolipoproteins B/genetics , Apolipoproteins C/genetics , DNA/drug effects , Gemfibrozil/pharmacology , Adult , Apolipoprotein A-I , Apolipoprotein C-III , Cholesterol, HDL/blood , Cholesterol, HDL/drug effects , Cholesterol, LDL/blood , Cholesterol, LDL/drug effects , DNA/genetics , Humans , Male , Middle Aged , Polymorphism, Restriction Fragment Length , Triglycerides/bloodABSTRACT
In the Helsinki Heart Study 2,590 subjects (63.5% of total) had a type IIa hyperlipoproteinemia at screening. Baseline low-density lipoprotein (LDL) cholesterol (mean 193 mg/dl; 5 mmol/liter) and high-density lipoprotein (HDL) cholesterol (mean 50.2 mg/dl; 1.3 mmol/liter) showed no statistical correlation (r = 0.046). Both the placebo (1,293 patients) and gemfibrozil groups (1,297 patients) were divided into tertiles by baseline HDL and LDL cholesterol to determine the relative predictive risk of developing coronary artery disease. In a population with elevated LDL cholesterol, it is significant that the lipoprotein fraction with the greatest predictive value was HDL cholesterol. The severity of LDL cholesterol elevation did not provide any differential predictive value for coronary artery disease.
