Glutamine/histidine polymorphism in apo A-IV affects plasma concentrations of lipoprotein(a) and fibrin split products in coronary heart disease patients.
A glutamine/histidine 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 fibrinolytic 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.
von Eckardstein
A
A
Institut für Klinische Chemie und Laboratoriumsmedizin, Westfälische Wilhelms-Universität Münster, FRG.
Heinrich
J
J
Funke
H
H
Schulte
H
H
Schönfeld
R
R
Köhler
E
E
Steinmetz
A
A
Assmann
G
G
D001054:Apolipoproteins A / Q000235:genetics*; D003327:Coronary Disease / Q000097:blood* / Q000209:etiology; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis*; D005973:Glutamine / Q000032:analysis*; D006487:Hemostasis; D006639:Histidine / Q000032:analysis*; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood* / Q000235:genetics; D008297:Male; D011110:Polymorphism, Genetic; D011973:Receptors, LDL / Q000235:genetics
D001054:Apolipoproteins A; D005338:Fibrin Fibrinogen Degradation Products; D017270:Lipoprotein(a); D011973:Receptors, LDL; C022205:apolipoprotein A-IV; D005973:Glutamine; D006639:Histidine