Atherosclerotic disease in marked hyperalphalipoproteinemia. Combined reduction of cholesteryl ester transfer protein and hepatic triglyceride lipase.
Hyperalphalipoproteinemia (HALP) has been regarded as a beneficial state accompanied by a longevity syndrome. However, we reported the cases of markedly hyperalphalipoproteinemic subjects with juvenile corneal opacification. The patients had reduced postheparin hepatic triglyceride lipase (HTGL) activities, and one of them has recently been identified to be homozygous for a missense mutation in exon 15 (D442: G) in the cholesteryl ester transfer protein (CETP) gene. In the current study, to elucidate the clinical significance of and atherogenicity in marked HALP, we determined the incidence of atherosclerotic cardiovascular disease (ACD) in patients with marked HALP and characterized the lipoprotein abnormalities in those who had ACD, focusing especially on CETP and HTGL. The subjects were 201 patients (111 males and 90 females) with marked HALP ( > or = 2.58 mmol/L [100 mg/dL]), 67% of whom were demonstrated to have the CETP gene mutations in the intron 14 splice donor site or in exon 15. Their mean age was 54 +/- 15 years. Plasma levels of total cholesterol, HDL cholesterol, and triglyceride in all subjects were 6.28 +/- 1.78, 3.15 +/- 0.90, and 1.08 +/- 0.53 mmol/L, respectively. Ten of the male patients (9.0%) and two of the female patients (2.2%) had apparent ACD such as myocardial infarction, angina pectoris, and peripheral vascular diseases. Ten patients with HALP who had ACD were identified to be heterozygotes for CETP deficiency. To further clarify the characteristics of marked HALP in patients with ACD, we compared the plasma lipids, lipoproteins, CETP, and HTGL activities between heterozygotes for CETP deficiency who were with and without ACD.
Hirano
K
K
Second Department of Internal Medicine, Osaka University Medical School Suita, Japan.
Yamashita
S
S
Kuga
Y
Y
Sakai
N
N
Nozaki
S
S
Kihara
S
S
Arai
T
T
Yanagi
K
K
Takami
S
S
Menju
M
M
D000328:Adult; D000368:Aged; D001053:Apolipoproteins / Q000378:metabolism; D001161:Arteriosclerosis / Q000097:blood* / Q000150:complications; D015415:Biomarkers; D002352:Carrier Proteins / Q000097:blood* / Q000235:genetics; D053480:Cholesterol Ester Transfer Proteins; D005260:Female; D006023:Glycoproteins; D006801:Humans; D006951:Hyperlipoproteinemias / Q000097:blood* / Q000150:complications; D008049:Lipase / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009154:Mutation
D001053:Apolipoproteins; D015415:Biomarkers; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; D008049:Lipase