title: The factor V R2 allele: risk of venous thromboembolism, factor V levels and resistance to activated protein C.
abstract: Case-control studies have yielded conflicting results regarding the relative risk of venous thromboembolism associated with the factor V R2 allele. We calculated odds ratios in 581 patients and 469 age-matched controls. The odds ratio for the R2 allele in patients relative to controls was 1.21 (95% CI 0.84 to 1.74). These results do not support the hypothesis that the R2 allele is a risk factor for venous thromboembolism. There was no relationship between factor V levels and R2 carrier status. Normalised APC sensitivity ratios were not lower in carriers of the R2 allele. In an in vitro model progressive APC resistance was observed with factor V levels of 60% and less but ratios less than 2.4 (equivalent to a normalised ratio of 0.73) did not occur until factor V levels were less than 20%. The relationship between APC resistance and factor V level was not observed in a factor VIII-independent model.
authors.affiliation: Department of Haematology, Addenbrooke's NHS Trust, Cambridge, United Kingdom.
authors.forename: R
authors.initials: R
authors.lastname: Luddington
authors.forename: A
authors.initials: A
authors.lastname: Jackson
authors.forename: S
authors.initials: S
authors.lastname: Pannerselvam
authors.forename: K
authors.initials: K
authors.lastname: Brown
authors.forename: T
authors.initials: T
authors.lastname: Baglin
mesh_terms: D020016:Activated Protein C Resistance / Q000097:blood / Q000150:complications / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D019943:Amino Acid Substitution; D016022:Case-Control Studies; D005165:Factor V / Q000009:adverse effects / Q000235:genetics* / Q000378:metabolism; D005166:Factor V Deficiency / Q000097:blood; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010314:Partial Thromboplastin Time; D017354:Point Mutation; D012307:Risk Factors; D013923:Thromboembolism / Q000097:blood* / Q000453:epidemiology / Q000235:genetics; D020246:Venous Thrombosis / Q000097:blood / Q000453:epidemiology / Q000235:genetics
chemical_list: C095381:factor V Leiden; D005165:Factor V