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Restriction Isotyping of Apoprotein E
- Georgetown University Medical Center, Washington, DC 20007. National Heart, Lung, and Blood Institute, Bethesda, MD 20892.
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TO THE EDITOR:
We address an issue raised by Walden and Hegele [1] on the specificity of the very-low-density lipoprotein (VLDL) cholesterol-to-triglyceride ratio as a characteristic of type III hyperlipidemia (a ratio > 0.30 is considered characteristic [2]). Currently, dietary modification and lipid-lowering drugs are often used before underlying genetic defects in hyperlipidemic patients are evaluated. We assessed the VLDL-to-triglyceride ratio with and without lipid-lowering therapy to determine whether this ratio remains a reliable persistent marker of the underlying genetic defect. We reviewed charts of patients with the E2/E2 isoform and characteristics of type III hyperlipidemia who were studied by the Molecular Disease Branch of the National Heart, Lung, and Blood Institute of the National Institutes of Health. The fasting, untreated lipid levels of the 17 patients showed VLDL cholesterol levels of 349 ±336 mg/dL and fasting triglyceride concentrations of 756 ±549 mg/dL. The VLDL cholesterol-to-triglyceride ratio was 0.44 ±0.15. The patients had an average of 5 ±1 repeated full lipid profiles while receiving various forms of lipid-lowering therapy. The patients' VLDL cholesterol levels decreased by 68% (P = 0.01), and their triglyceride concentrations decreased by 59% (P = 0.004). The VLDL cholesterol-to-triglyceride ratio decreased by 16% (P = 0.1). Seventy-four ratios were measured; the baseline and mean ratios are shown in Figure 1. Of 17 patients, 3 had a baseline ratio of less than 0.30, and 5 had a mean treatment ratio of less than 0.30. This low ratio was observed in one third of the lipid profiles drawn (28 of 74 ratios), affecting about one half of the patients (8 of 17 patients) at one or more of their visits.
The clinical importance of these data is that if patients were screened on one of these visits, the diagnosis might not be suspected. Family screening and treatment would not be done, with deleterious effects. Therefore, a single ratio at baseline or during therapy is not a reliable marker for disease. Apolipoprotein E restriction isotyping may become an additional method in screening for the risk for type III hyperlipidemia [1], and the limitations of the VLDL cholesterol-to-triglyceride ratio should be appreciated.
The Editors welcome submissions for possible publication in the Letters section. Authors of letters should:
•Include no more than 300 words of text, three authors, and five references
•Type with double-spacing
•Send three copies of the letter, an authors' form signed by all authors, and a cover letter describing any conflicts of interest related to the contents of the letter.
Letters commenting on an Annals article will be considered if they are received within 6 weeks of the time the article was published. Only some of the letters received can be published. Published letters are edited and may be shortened; tables and figures are included only selectively. Authors will be notified that the letter has been received. If the letter is selected for publication, the author will be notified about 3 weeks before the publication date. Unpublished letters cannot be returned.
Annals welcomes electronically submitted letters.
- Copyright ©2004 by the American College of Physicians
