Cited by 277Lipoproteins and Cardiovascular HealthParaoxonase enzyme and polymorphismsLipid metabolism and disorders

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Genetic Cholesteryl Ester Transfer Protein Deficiency Is Extremely Frequent in the Omagari Area of Japan: Marked Hyperalphalipoproteinemia Caused by CETP Gene Mutation Is Not Associated With Longevity

Hirano, Ken-ichi, Yamashita, Shizuya, Nakajima, Norimichi, Arai, Takeshi, Maruyama, Takao, Yoshida, Yu, Ishigami, Masato, Sakai, Naohiko, Kameda-Takemura, Kaoru, Matsuzawa, Yuji·1997·Arteriosclerosis, Thrombosis, and Vascular Biology

DOI 10.1161/01.atv.17.6.1053

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Abstract

Abstract Low levels of HDL cholesterol have been clearly demonstrated to be associated with an increased incidence of coronary heart disease, strongly suggesting that HDL particles have an antiatherogenic function. However, little information has been available concerning the atherogenicity of a marked hyperalphalipoproteinemia (HALP). There is no agreement about whether plasma cholesteryl ester transfer protein (CETP) deficiency is associated with an antiatherogenic state or not, although this disorder was reported to be one of the major causes of marked HALP. In the current study, we have found a unique area (Omagari City, Akita Prefecture, Japan) where CETP deficiency caused by a G-to-A mutation at the 5′ splice donor site of intron 14 in the CETP gene is extremely frequent. In Omagari City, the mutation was detected more than 20 times more frequently and the prevalence of a marked HALP with plasma HDL cholesterol ≥2.58 mmol/L (100 mg/dL) was 5 to 10 times higher than in other areas of Japan. This discovery has made it possible to perform a large population-based study concerning the atherogenicity of a marked elevation of HDL cholesterol in a genetically more homogeneous population. There was a statistically significant U-shaped relationship between HDL cholesterol levels and the incidence of ischemic changes in electrocardiograms. In cases of HDL cholesterol <1.81 mmol/L (70 mg/dL), the incidence increased in proportion to the levels of HDL cholesterol. The frequency of the CETP gene mutation was higher in patients with coronary heart disease than in healthy control subjects. In subjects aged >80 years, the prevalence of both marked HALP and the intron 14 splicing defect was significantly lower than in the younger generation. The current study indicated for the first time that a marked HALP caused by CETP gene mutation may not represent a longevity syndrome, suggesting the importance of reevaluation of the clinical significance and pathophysiology of a marked HALP.

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Authors: Hirano, K.-I., Yamashita, S., Nakajima, N., Arai, T., Maruyama, T., Yoshida, Y., Ishigami, M., Sakai, N., Kameda-Takemura, K., & Matsuzawa, Y.
Affiliations: The University of Osaka (JP)
From the Second Department of Internal Medicine, Osaka University Medical School (K-i.H., S.Y., T.A., T.M., Y.Y., M.I., N.S., K.K.-T., Y.M.), and the Nakajima Clinic, Akita (N.N.), Japan.
ORCID: Hirano, Ken-ichi
Yamashita, Shizuya
Arai, Takeshi
Maruyama, Takao
Yoshida, Yu
Venue: Arteriosclerosis, Thrombosis, and Vascular Biology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 1997-06
Volume: 17
Issue: 6
Pages: 1053-1059
ISSN: 1079-5642 (ISSN-L)
1524-4636
DOI: 10.1161/01.atv.17.6.1053
OpenAlex: W2151720705
Cited by: 275
References: 40
Citations by year: 2026: 3 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 3 · 2021: 7 · 2020: 4 · 2019: 2 · 2018: 5 · 2017: 5 · 2016: 9 · 2015: 11 · 2014: 9 · 2013: 11 · 2012: 15
FWCI: 14.93
Type: journal article
Language: en
Open access: closed
Locations: Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Keywords: hyperalphalipoproteinemia, HDL cholesterol, coronary artery disease, atherogenicity, genetic prevalence
MeSH terms: Aged, Carrier Proteins, Female, Glycoproteins, Humans, Japan, Lipid Metabolism, Inborn Errors, Lipoproteins, HDL, Longevity, Male, Middle Aged, Cholesterol Ester Transfer Proteins

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Genetic Cholesteryl Ester Transfer Protein Deficiency Is Extremely Frequent in the Omagari Area of Japan: Marked Hyperalphalipoproteinemia Caused by CETP Gene Mutation Is Not Associated With Longevity

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