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Cited by 861

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Increased High-Density Lipoprotein Levels Caused by a Common Cholesteryl-Ester Transfer Protein Gene Mutation

Open access
Inazu, Akihiro, Brown, Maryanne L., Hesler, Charles B., Agellon, Luis B., Koizumi, Junji, Takata, Koki, Maruhama, Yoshisuke, Mabuchi, Hiroshi, Tall, Alan R.·1990·New England Journal of Medicine
DOI 10.1056/nejm199011013231803
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Abstract

BACKGROUND AND METHODS: The plasma cholesteryl-ester transfer protein (CETP) catalyzes the transfer of cholesteryl esters from high-density lipoprotein (HDL) to other lipoproteins. We recently described a Japanese family with increased HDL levels and CETP deficiency due to a splicing defect of the CETP gene. To assess the frequency and phenotype of this condition, we screened 11 additional families with high HDL levels by means of a radioimmunoassay for CETP and DNA analysis. RESULTS: We found the same CETP gene mutation in four families from three different regions of Japan. Analysis of restriction-fragment-length polymorphisms of the mutant CETP allele showed that all probands were homozygous for the identical haplotype. Family members homozygous for CETP deficiency (n = 10) had moderate hypercholesterolemia (mean total cholesterol level [+/- SD], 7.01 +/- 0.83 mmol per liter), markedly increased levels of HDL cholesterol (4.24 +/- 1.01 mmol per liter) and apolipoprotein A-I, and decreased levels of low-density lipoprotein cholesterol (1.99 +/- 0.80 mmol per liter) and apolipoprotein B. Members heterozygous for the deficiency (n = 20), whose CETP levels were in the lower part of the normal range, had moderately increased levels of HDL cholesterol and apolipoprotein A-I and an increased ratio of HDL subclass 2 to HDL subclass 3, as compared with unaffected family members (1.5 +/- 0.8 vs. 0.7 +/- 0.4). CETP deficiency was not found in six unrelated subjects with elevated HDL cholesterol levels who were from different parts of the United States. CONCLUSIONS: CETP deficiency appears to be a frequent cause of increased HDL levels in the population of Japan, possibly because of a founder effect. The results that we observed in heterozygotes suggest that CETP normally plays a part in the regulation of levels of HDL subclass 2. There was no evidence of premature atherosclerosis in the families with CETP deficiency. In fact, the lipoprotein profile of persons with CETP deficiency is potentially antiatherogenic and may be associated with an increased life span.

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Metadata

Authors
Inazu, A., Brown, M. L., Hesler, C. B., Agellon, L. B., Koizumi, J., Takata, K., Maruhama, Y., Mabuchi, H., & Tall, A. R.
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
1990-11
Volume
323
Issue
18
Pages
1234-1238
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejm199011013231803
OpenAlex
W2336122760
Cited by
861
References
1
FWCI
24.59
Type
journal article
Language
en
Open access
bronze

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