title: Co-inheritance of the 20210A allele of the prothrombin gene increases the risk of thrombosis in subjects with familial thrombophilia.
abstract: The presence of the 20210A allele of the prothrombin (PT) gene has recently been shown to be a risk factor for venous thromboembolism. This is probably mediated through increased plasma prothrombin levels. The aim of this study was to compare the prevalence of the prothrombin 20210A allele in control subjects and in subjects with recognised thrombophilia and to establish whether the additional inheritance of the PT 20210A allele is associated with an increased risk of venous thromboembolism. 101 subjects with a history of venous thromboembolism and diagnosed as having either factor V Leiden (R506Q) or heritable deficiencies of protein C, protein S or antithrombin were studied. The prevalence of the PT 20210A allele in this group was compared with the results obtained for 150 control subjects. In addition, the relationships were examined between genetic status and the number of documented thromboembolic episodes, and between plasma prothrombin levels and possession of the PT 20210A allele. 8 (7.9%) of the 101 patients were also heterozygous for the PT 20210A allele. This compares with 0.7% in the control subjects (p = 0.005). After exclusion of patients on warfarin, the mean plasma prothrombin of 113 subjects without 20210A was 1.09 U/ml, as compared with 1.32 U/ml in 8 with the allele (p = 0.0002). Among the 101 patients with either factor V Leiden, protein S deficiency, protein C deficiency or antithrombin deficiency, the age adjusted mean (SD) number of venous thromboembolic episodes at diagnosis was 3.7 (1.5) in those with the PT 20210A allele, as compared with 1.9 (1.1) in those without (p = 0.0001). We have demonstrated that the prevalence of the PT 20210A allele is significantly greater in subjects with venous thrombosis and characterised heritable thrombophilia than in normal control subjects and that the additional inheritance of PT 20210A is associated with an increased risk of venous thromboembolism. We have also confirmed that plasma prothrombin levels are significantly greater in subjects possessing the PT 20210A compared with those who do not.
authors.affiliation: University of Sheffield, Royal Hallamshire Hospital, Department of Medicine and Pharmacology, UK.
authors.forename: M
authors.initials: M
authors.lastname: Makris
authors.forename: F E
authors.initials: FE
authors.lastname: Preston
authors.forename: N J
authors.initials: NJ
authors.lastname: Beauchamp
authors.forename: P C
authors.initials: PC
authors.lastname: Cooper
authors.forename: M E
authors.initials: ME
authors.lastname: Daly
authors.forename: K K
authors.initials: KK
authors.lastname: Hampton
authors.forename: P
authors.initials: P
authors.lastname: Bayliss
authors.forename: I R
authors.initials: IR
authors.lastname: Peake
authors.forename: G J
authors.initials: GJ
authors.lastname: Miller
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D005796:Genes; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation / Q000235:genetics* / Q000502:physiology; D011516:Prothrombin / Q000235:genetics* / Q000378:metabolism; D011655:Pulmonary Embolism / Q000150:complications / Q000235:genetics; D012307:Risk Factors; D019851:Thrombophilia / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D013924:Thrombophlebitis / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D011516:Prothrombin