Background Previous studies have suggested that the variantapolipoprotein (apo) allele apo A-IV-2 may influence the responseof the plasma cholesterol concentration to dietary cholesterol.
Methods We measured plasma lipids and lipoproteins in 11 subjectswho were heterozygous for the apo A-IV-2 allele (apo A-IV-1/2heterozygotes) and a control group of 12 subjects who were homozygousfor the common apo A-IV allele (apo A-IV-1/1 homozygotes) inan outpatient dietary-modification study. (Approximately onein seven persons in the United States is a heterozygote.) Thesubjects consumed a low-cholesterol diet (about 200 mg [0.5mmol] of cholesterol per day) during a two-week run-in period;daily cholesterol intake was then increased to approximately1100 mg (2.8 mmol) by the addition of four egg yolks per day.
Results The fat intake and the ratio of polyunsaturated to saturatedfat were similar in the two groups throughout the study. Afterthree weeks of egg intake, the mean plasma total cholesterolincreased by 22 mg per deciliter (0.57 mmol per liter) in theapo A-IV-1/1 group, but by only 6 mg per deciliter (0.15 mmolper liter) in the apo A-IV-1/2 group (P = 0.05). The mean plasmalow-density lipoprotein cholesterol increased by 19 mg per deciliter(0.49 mmol per liter) in the apo A-IV-1/1 group, but by only1 mg per deciliter (0.03 mmol per liter) in the apo A-IV-1/2group (P = 0.03). There were no changes in the plasma triglycerideor high-density lipoprotein cholesterol concentrations in eithergroup.
Conclusions The apo A-IV-2 allele attenuates the hypercholesterolemicresponse to the short-term ingestion of a very-high-cholesteroldiet and may partially account for the heterogeneous responseto dietary cholesterol. However, cholesterol intake in thisstudy was more than twice that of the general population; whetherthe apo A-IV-2 allele alters responsiveness at lower levelsof cholesterol intake remains to be determined.
Source Information
From the Department of Internal Medicine, Section of Gastroenterology, Bowman Gray School of Medicine, Winston-Salem, N.C.
Address reprint requests to Dr. Weinberg at the Bowman Gray School of Medicine, Medical Center Blvd., Winston-Salem, NC 27257.
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