ATTENUATED HYPERCHOLESTEROLEMIC RESPONSE TO A HIGH-CHOLESTEROL DIET IN SUBJECTS HETEROZYGOUS FOR THE APOLIPOPROTEIN A-IV-2 ALLELE

Background. Previous studies have suggested that the variant apolipoprotein (ape) allele apo A-IV-2 may influence the response of the plasma cholesterol concentration to dietary cholesterol. Methods. We measured plasma lipids and lipoproteins in 11 subjects who were heterozygous for the apo A-IV-2 allele (ape A-IV-1/2 heterozygotes) and a control group of 12 subjects who were homozygous for the common apo A-IV allele (ape A-IV-III homozygotes) in an outpatient dietary-modification study. (Approximately one in seven persons in the United States is a heterozygote.) The subjects consumed a low-cholesterol diet (about 200 mg [0.5 mmol] of cholesterol per day) during a two-week run-in period; daily cholesterol intake was then increased to approximately 1100 mg (2.8 mmol) by the addition of four egg yolks per day. Results. The fat intake and the ratio of polyunsaturated to saturated fat were similar in the two groups throughout the study. After three weeks of egg intake, the mean plasma total cholesterol increased by 22 mg per deciliter (0.57 mmol per liter) in the ape A-IV-1/1 group, but by only 6 mg per deciliter (0.15 mmol per liter) in the apo A-IV-1/2 group (P = 0.05). The mean plasma low-density lipoprotein cholesterol increased by 19 mg per deciliter (0.49 mmol per liter) in the apo A-IV-1/1 group, but by only 1 mg per deciliter (0.03 mmol per liter) in the ape A-IV-1/2 group (P = 0.03). There were no changes in the plasma triglyceride or high-density lipoprotein cholesterol concentrations in either group. Conclusions. The apo A-IV-2 allele attenuates the hypercholesterolemic response to the short-term ingestion of a very-high-cholesterol diet and may partially account for the heterogeneous response to dietary cholesterol. However, cholesterol intake in this study was more than twice that of the general population; whether the apo A-IV-2 allele alters responsiveness at lower levels of cholesterol intake remains to be determined.