Abstract
The existence of two types of thrombomodulin (TM) amino acid dimorphism (Ala 455 or
Val 455) for the development of unexplained thrombophilia is controversial. We have
identified the Val 455-TM allele in one patient with severe preeclampsia and the Ala
455-TM allele in another patient with the same disease. We evaluated distributions
of the two types of alleles among 20 normal pregnant women and 18 patients with severe
early-onset preeclampsia using polymerase chain reaction (PCR) amplification of genomic
DNA and hybridization of allele-specific oligonucleotide probes to the amplified DNA.
All possible genotypes (Val/Val, Val/Ala, Ala/Ala) were found in each group. Recombinant
TM of each genotype was produced by Cos-I cells, and Val 455-TM and Ala 455-TM alleles
were equally active in protein C activation. The frequency of each allele was the
same in the normal and the patient groups, but the distribution of each genotype in
the patients was different from that of normal pregnant women. We conclude that these
two types of TM alleles are functionally equivalent. This study suggests that TM polymorphism
may be involved in the pathogenesis of severe early-onset preeclampsia.
Keywords:
Thrombomodulin - DNA polymorphism - severe early-onset preeclampsia - protein C-activating
cofactor activity - dot hybridization - frequency of allele
