Affiliation:
1. From the Hemostasis and Thrombosis Research Center (C.A.S., F.R.R., R.M.B., P.H.R.) and the Department of Clinical Epidemiology (T.K., F.R.R.), University Hospital Leiden, the Netherlands.
Abstract
Abstract
Protein C is a vitamin K–dependent zymogen of a serine protease that inhibits blood coagulation by proteolytic inactivation of factors Va and VIIIa. Individuals with protein C deficiency are at risk for thrombophlebitis, deep-vein thrombosis, and pulmonary embolism. Genetic analysis of a number of randomly chosen healthy individuals revealed three polymorphisms, C/T at −654, A/G at −641, and A/T at −476, in the protein C promoter region. To investigate whether these genetic variations associate with the plasma protein C level, we determined the genotype for the three polymorphisms and measured plasma protein C levels in 240 individuals not deficient in protein C. The mean protein C level of these individuals was 103%. Interestingly, individuals with the homozygous CGT genotype (n=40) had a mean protein C level of 94%, whereas individuals with a homozygous TAA genotype (n=28) had a mean protein C level of 116%. This difference in mean protein C levels between the CGT and TAA groups (
P
<.001) could not be explained by environmental factors known to influence protein C levels in the normal population. Plasma factor II and factor X levels did not differ between the two groups, which makes a difference in liver function an unlikely cause. Finally, we tested whether the genotype associated with lower protein C levels is associated with higher thrombotic risks. This analysis showed that compared with the genetic variant associated with higher protein C levels (TT/AA/AA), the genetic variant associated with lower protein C levels (CC/GG/TT genotype) is indeed a risk factor for thrombosis (OR, 1.6; 95% confidence interval, 1.0 to 2.5).
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine
Cited by
97 articles.
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