Glutamine/Histidine Polymorphism in Apo A‐IV Affects Plasma Concentrations of Lipoprotein(a) and Fibrin Split Products in Coronary Heart Disease Patients
作者:
Arnold Eckardstein,
Jiirgen Heinrich,
Harald Funke,
Helmut Schulte,
Rainer Schonfeld,
Ekkehart K6hler,
Annin Steinmetz,
Gerd Assmann,
期刊:
Arteriosclerosis and Thrombosis: A Journal of Vascular Biology
(OVID Available online 1993)
卷期:
Volume 13,
issue 2
页码: 240-246
ISSN:1049-8834
年代: 1993
出版商: OVID
关键词: apo A-IV polymorphism;lipoprotein(a);D-dimer;fibrinolysls;hemostasis;thrombosis;atherosclerosis
数据来源: OVID
摘要:
A glutamine/histldine polymorphism at residue 360 in apolipoprotein (apo) A-IV that generates two electrophoretically detectable isoforms, apo A-IV-1 and apo A-IV-2, affects the plasma concentration of lipoprotein(a) (Lp[a]) in a healthy population. To verify this unexpected association we analyzed the effect of the apo A-IV polymorphism on Lp(a) serum concentrations in 275 male coronary heart disease patients. Allele frequencies of apo A-IV-1 and apo A-IV-2 were 0.917 and 0.083, respectively. In addition, apo A-IV-1/2 heterozygotes showed a 30% lower geometric mean concentration of Lp(a) than apo A-IV-1/1 homozygotes in this study. The relative frequency of Lp(a) concentrations >20 mg/dl was significantly increased by a factor of 2.25 in apo A-IV-1/1 homozygotes. Other lipid parameters were not significantly affected by this apo A-IV polymorphism. Because of the relations between Lp(a) and the fibrinolytlc system, we also analyzed the effect of the apo A-IV polymorphism on hemostatic variables. Apo A-IV-1/2 heterozygosity was associated with a 70% higher geometric mean plasma concentration of D-dimer, i.e., proteolytic fragments of cross-linked fibrin. Plasma concentrations of prothrombin fragments F1+F2, fibrinogen, plasminogen, and plasminogen activator inhibitor-1 were unaffected. In conclusion, our results indicate a hitherto unappreciated role of the apo A-IV gene or a closely linked locus for the regulation of Lp(a) metabolism and hemostasis and also possibly for atherosclerosis and thrombosis.
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