Protein C 유전자의 Novel Splice Site Polymorphism (G3223T) 검색 가계의 유전양상과 변이 대립유전자 비율

Abstract

Background : Human protein C cDNA clones have been isolated from liver cDNA libraries and sequenced. A number of DNA sequence polymorphism re known to occur in protein C gene. These include A/T (-1476), C/T (-1654) and A/G (-1641) polymophisms within the promotor region. Methods : We have identified unique molecular events (G3223T) in two patients with thrombosis and acquired protein C deficiency due to oral anticoagulant therapy. The genetic analysis of 31 family members from two independent probands was performed to observe the genetic inheritance of G3223T variations and phenotypic plasma protein C levels. In addition, a total of 54 subjects, including 30 patients with thrombosis and 24 healthy subjects, were analyzed to estimate the allelic(G/T) frequencies in Korean and to see the possible difference between normal and patient groups. Results : The polymorphism(G3223T) at donor splice site of protein C gene was found in 12 of 31 family members from two independent probands. However, there was no association of this polymorphism with plasma protein C activity. Allelic frequencies of 96.3%(G) and 3.7%(T) were found in Korean population, which was not significantly different between normal and patient groups. Conclusions : We report a novel splice site polymorphic variation(G3223T) in two independent families, which seems to be rare but has no significance in association with protein C phenotypic levels or thrombotic risk.