Analysis of Thrombomodulin Gene Polymorphism in Women with Severe Early-Onset Preeclampsia

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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.

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