AN AMINO-ACID POLYMORPHISM IN HISTIDINE-RICH GLYCOPROTEIN (HRG) EXPLAINS 59-PERCENT OF THE VARIANCE IN PLASMA HRG LEVELS

A pedigree-based maximum likelihood method developed by Lange et al. ( 12) was used to study the contribution of a newly defined di-allelic p olymorphism in histidine-rich glycoprotein (HRG) to the plasma levels of HRG. In four families (n = 99) and 20 volunteers we found a heritab ility of 70%, an age effect of 3% and an effect of individual environm ental factors of 27%, These results are remarkably similar to the resu lts found in a previous parent-twin study in which a heritability of 6 9% and an effect of random environment of 31% was found. The overall g enetic 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 add ing up the effect of the two alleles that make up the phenotype. These results indicate a codominant inheritance pattern of HRG levels in wh ich the genetic influence can almost completely be ascribed to the add itive effect of the di-allelic HRG locus whereas only a small part is due to other loci.