RSS-Feed abonnieren
DOI: 10.1055/s-0038-1649972
An Amino Acid Polymorphism in Histidine-rich Glycoprotein (HRG) Explains 59% of the Variance in Plasma HRG Levels
Publikationsverlauf
Received 08. Mai 1995
Accepted after resubmission 17. August 1995
Publikationsdatum:
10. Juli 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/199506/lookinside/thumbnails/10-1055-s-0038-1649972-1.jpg)
Summary
A pedigree-based maximum likelihood method developed by Lange et al. (12) was used to study the contribution of a newly defined di-allelic polymorphism in histidine-rich glycoprotein (HRG) to the plasma levels of HRG. In four families (n = 99) and 20 volunteers we found a heritability of 70%, an age effect of 3% and an effect of individual environmental factors of 27%. These results are remarkably similar to the results found in a previous parent-twin study in which a heritability of 69% and an effect of random environment of 31% was found. The overall genetic influence in the present study can be subdivided into an effect of 59% by the HRG phenotype and 11% by residual genetic factors. The influence of the HRG phenotype of 59% can entirely be explained by adding up the effect of the two alleles that make up the phenotype. These results indicate a codominant inheritance pattern of HRG levels in which the genetic influence can almost completely be ascribed to the additive effect of the di-allelic HRG locus whereas only a small part is due to other loci.
-
References
- 1 Koide T. The primary structure of human histidine-rich glycoprotein and its functions as a modulator of coagulation and fibrinolysis. In: Fibrinolysis: Current Prospects. Gaffney PJ, Castellino FJ, Plow EF, Takada A. eds John Libbey Co; London: 1988. pp 55-63
- 2 Samama M, Conard J, Castel-Gatey M, Horrelou MH. Histidine-rich glycoprotein and deep venous thrombosis. In: Clinical Aspects of Fibrinolysis and Thrombolysis. Jespersen J, Kluft C, Korsgaard O. eds South Jutland University Press; Esbjerg: 1983. pp 163-73
- 3 Engesser L, Kluft C, Juhan-Vague I, Briät E, Brommer EJ P. Plasma histidine-rich glycoprotein and thrombophilia. Fibrinolysis Suppl (Suppl. 02) 1988: 43
- 4 Ehrenforth S, Aggören-Pürsüm V, Hach-Wanderle V, Scharrer I. Prevalence of elevated histidine-rich glycoprotein in patients with thrombophilia – a study of 695 patients. Thromb Haemost 1994; 71: 160-161
- 5 Engesser L, Kluft C, Briät E, Brommer EJ P. Familial elevation of plasma histidine-rich glycoprotein in a family with thrombophilia. Br J Haematol 1987; 67: 355-358
- 6 Anglées-Cano E, Gris JC, Loyau S, Schved JF. Familial association of high levels of histidine-rich glycoprotein and plasminogen activator inhibitor-1 with venous thromboembolism. J Lab Clin Med 1993; 121: 646-653
- 7 Castaman G, Ruggeri M, Burei F, Rodeghiero F. High levels of histidine- rich glycoprotein and thrombotic diathesis – report of 2 unrelated families. Thromb Res 1993; 69: 297-305
- 8 Hennis BC, van Boheemen PA, Koeleman BP C, Boomsma DI, Engesser L, Van Wees AG M, Novakova I, Brommer EJ P, Kluft C. Association of elevated histidine-rich glycoprotein (HRG) with a specific allele of the HRG gene in a family with thrombosis. Br J Haematol 1995; 89: 219-224
- 9 Hennis BC, Frants RR, Bakker E, Vossen RH A M, Frants RR, Van der Poort EW, Cox S, Meera Khan P, Spurr NK, Kluft C. Evidence for the absence of intron H of the histidine-rich glycoprotein gene: Genetic mapping and in situ localization of HRG chromosome 3q28-29. Genomics 1994; a 19: 195-197
- 10 Boomsma DI, Hennis BC, Van Wees AG M, Frants RR, Kluft C. A parent- twin study of plasma levels of histidine-rich glycoprotein (HRG). Thromb Haemost 1993; 70: 848-851
- 11 Hennis BC, van Boheemen PA, Wakabayashi S, Koide T, Hoffmann JJ M L, Kievit P, Dooijewaard G, Jansen JG, Kluft C. Identification and genetic analysis of a common molecular variant of histidine-rich glycoprotein with a difference of 2KD in apparent molecular weight. Thromb Haemost. in press
- 12 Lange K, Westlake J, Spence MA. Extensions to pedigree analysis III Variance components by the scoring method. Ann Hum Gen 1976; 39: 485-491
- 13 De Bart AC W, Hennis BC, Havelaar AC, Kluft C. Variability in information from a single venapuncture in healthy volunteers: analysis of the haemostatic variables fibrinogen, plasminogen activator inhibitor (PAI) activity and histidine-rich glycoprotein (HRG). Fibrinolysis 1992; Suppl (Suppl. 03) 81-82
- 14 Mancini G, Carbonara AD, Heremans JF. Immunochemical quantitation of antigens by single radial immunodiffusion. Immunochemistry 1965; 2: 235-254
- 15 Lijnen HR, Hoylaerts M, Collen D. Isolation and characterization of a human plasma protein with affinity for the lysine binding sites in plasminogen Role in the regulation of fibrinolysis and identification as histidine-rich glycoprotein. J Biol Chem 1980; 255: 10214-10222
- 16 Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970; 227: 680-685
- 17 Lange K, Weeks D, Boehnke M. Programs for pedigree analysis: MENDEL, FISHER and dGENE. Gen Epidemiol 1988; 5: 471-472
- 18 Hoffmann JJ M L, Hennis BC, Kluft C, Vijgen M. Hereditary increase of plasma histidine-rich glycoprotein associated with abnormal heparin binding (HRG Eindhoven). Thromb Haemost 1993; 70: 894-899
- 19 Lijnen HR, Jacobs G, Collen D. Histidine-rich glycoprotein in a normal and clinical population. Thromb Res 1981; 22: 519-523