In:
Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 17, No. 11 ( 1997-11), p. 2837-2842
Abstract:
Abstract We studied the molecular basis of low hepatic lipase (HL) activity in normolipidemic male patients with angiographically documented coronary artery disease (CAD). In 18 subjects with a lowered HL activity ( 〈 225 mU/mL), all nine exons of the HL gene and part of the promoter region (nucleotides −524 to +7) were sequenced. No structural mutations in the coding part of the HL gene were found, but 50% of the subjects showed a C-to-T substitution at nucleotide −480. Screening for the base substitution in 782 patients yielded an allele frequency of 0.213 (297 heterozygotes, 18 homozygotes). In a group of 316 nonsymptomatic control subjects, the allele frequency was 0.189, which is significantly less than in the CAD patients ( P =.035). In the CAD patients, the C-to-T substitution was associated with a lowered lipase activity (heterozygotes −15%, homozygotes −20%). The patients were divided into quartiles on the basis of HL activity. Sixty percent (allele frequency 0.32) of the patients in the lowest quartile (HL activity 〈 306 mU/mL) had the gene variant against 27% (allele frequency 0.14) in the highest quartile (HL activity 〉 466 mU/mL). In the noncarriers, but not in the carriers, HL activity was related with plasma insulin, being increased at higher insulin concentration. Homozygous carriers had a significantly higher HDL cholesterol level than noncarriers (1.13±0.28 mmol/L versus 0.92±0.22 mmol/L, P 〈 .02). Our results show that a C-to-T substitution at −480 of the HL promoter is associated with a lowered HL activity. The base substitution, or a closely linked gene variation, may contribute to the variation in HL activity and affect plasma lipoprotein metabolism.
Type of Medium:
Online Resource
ISSN:
1079-5642
,
1524-4636
DOI:
10.1161/01.ATV.17.11.2837
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
1997
detail.hit.zdb_id:
1494427-3
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