Genotypic variation in the promoter region of the protein C gene is associated with plasma protein C levels and thrombotic risk

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