The prevalence of heterozygous F12 mutations in Chinese population and its relevance to incidents of thrombosis

BACKGROUND: The contribution of moderate coagulation factor XII (FXII) deficiency to development of thromboembolism is still undetermined. We have tried to show the relevance of FXII deficiency to incidences of venous thrombosis by exploring the prevalence of F12 gene mutations in Chinese patients with thrombotic disorders. METHODS: One hundred and six patients with venous thromboembolism (VTE) and 220 healthy controls were enrolled in study. The coding region and flanking sequences of F12 gene were amplified and sequenced to identify genetic variances. Patients with F12 mutations were also screened for other thrombotic risk factors. RESULTS: Heterozygous F12 gene mutations were identified in 6 individuals with VTE and 10 healthy controls. Q336X and R66W were found in two healthy individuals; D291E was identified in a patient with DVT; and A343P was a recurrent mutation with a prevalence of 4.7% (5/106) in patient group and 3.6%(8/220) in healthy control. The prevalence of heterozygous mutations between the two groups had no significant difference. The association of A343P mutations with VTE was weak with an OR of 1.31 (95% CI 0.42-4.11). No other thrombophilia risk factors screened were positive in patients harboring heterozygous F12 mutations. CONCLUSIONS: There were conflicting theories about the relationship between FXII deficiency and thrombosis formation. Heterozygous F12 mutation decreases the plasma FXII activity approximately by half and cause moderate FXII deficiency. Although multiple mutations were identified in both groups, the link between F12 heterozygous mutation and development of thrombotic disorders is weak and further studies are warranted to clarify their relationship.