A 2-ALLELE POLYMORPHISM IN PROTEIN-C INHIBITOR WITH VARYING FREQUENCIES IN DIFFERENT ETHNIC POPULATIONS

cDNAs for protein C inhibitor (PCI), prepared from human liver RNA, co ntained two forms of PCI, designated PCIA and PCI*B-1, While PCI*A is identical to the published PCI sequence, PCIB differs in 4 of 1221 b p and two amino acids, A36V and K86E. Frequencies for the PCIB allele , determined from genomic DNA, differed among ethnic groups. Frequency distribution and historical migration of modern man suggest that PCI A arose from the PCIB allele. Antigen levels in plasma homozygous for PCIA or PCI*B equalled that of pooled normal plasma. K86E in PCI*B c auses a charge alteration in helix D which is likely involved in hepar in binding in antithrombin III but not likely involved in glycosaminog lycan binding in PCI. Kinetic studies showed that plasmas homozygous f or PCIA 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.