A two-allele polymorphism in protein C inhibitor with varying frequencies in different ethnic populations.
cDNAs for protein C inhibitor (PCI), prepared from human liver RNA, contained two forms of PCI, designated PCI*A and PCI*B. While PCI*A is identical to the published PCI sequence, PCI*B differs in 4 of 1221 bp and two amino acids, A36V and K86E. Frequencies for the PCI*B allele, determined from genomic DNA, differed among ethnic groups. Frequency distribution and historical migration of modern man suggest that PCI*A arose from the PCI*B allele. Antigen levels in plasma homozygous for PCI*A or PCI*B equalled that of pooled normal plasma. K86E in PCI*B causes a charge alteration in helix D which is likely involved in heparin binding in antithrombin III but not likely involved in glycosaminoglycan binding in PCI. Kinetic studies showed that plasmas homozygous for PCI*A and PCI*B are similar in their APC inhibiting properties and in their heparin sensitivity, consistent with the idea that helix D in PCI is not involved in heparin binding.
Radtke
K P
KP
Department of Molecular Medicine, Scripps Research Institute, La Jolla, CA, USA.
Greengard
J S
JS
Fernández
J A
JA
Villoutreix
B O
BO
Griffin
J H
JH
D000483:Alleles; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D003196:Computer Graphics; D005787:Gene Frequency; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D018046:Protein C Inhibitor / Q000235:genetics* / Q000378:metabolism; D044465:White People / Q000235:genetics*
D018046:Protein C Inhibitor; D006493:Heparin