A common C -> T polymorphism at nt 46 in the promoter region of coagulation factor XII is associated with decreased factor XII activity

Coagulation factor XII (FXII) deficiency is rarely found to be associated w ith bleeding, but single reports demonstrated thromboembolic events in FXII -deficient patients. Currently, the biological role of FXII is still discus sed controversially. It is well known that plasma levels of FXII show great interindividual variability. Recently, it has been demonstrated that a fre quently occurring CIT polymorphism in the FXII promoter region at nucleotid e (nt) 46 is associated with lower plasma FXII activity levels in Orientals . In our study, we evaluated the frequency of this polymorphism in a random ly selected sample of newborns and investigated whether this C --> T polymo rphism also contributes to the frequently observed moderate FXII deficiency in Europeans. We developed a new mutagenically separated polymerase chain reaction assay (MS PCR), which allows mutation detection without the use of restriction enzymes. Among 100 healthy newborns, we found 64% homozygous c arriers of the wildtype FXII 46C allele, 29% were heterozygous for FXII C46 T, and 7% homozygous for FXII 46T. Evaluation of plasma FXII activity and g enotype in 80 randomly selected and unrelated individuals revealed a highly statistically significant (P < .001) association of the FXII 46T allele wi th reduced FXII plasma activity. Individuals carrying the homozygous FXII 4 6C genotype had a mean of 1.17 U/ml (+/-0.31 U/ml), individuals heterozygou s for FXII C46T showed a mean of 0.70 U/ml (+/-0.31 U/ml), and subjects hom ozygous for FXII 46T had only 0.44 U/ml (+/-0.10 U/ml) plasma FXII activity . (C) 2001 Elsevier Science Ltd. All rights reserved.