title: Family history of venous thromboembolism as a risk factor and genetic research tool.
abstract: Familial clustering of venous thromboembolism (VTE) was described as far back as 1905 by Briggs. Although Egeberg discovered inherited deficiency of antithrombin in 1965, it was not until Dahlbäck discovered resistance to activated protein C in 1993 that it became clear that genetic factors are common risk factors of VTE. Several genes have been linked to familial aggregation of VTE and genome-wide association studies have found several novel gene loci. Still, it has been estimated that much of the heritability for VTE remains to be discovered. Family history (FH) of VTE is therefore still important to determine whether a patient has an increased genetic risk of VTE. FH has the potential to represent the sum of effects and interactions between environmental and genetic factors. In this article the design, methodology, results, clinical and genetic implications of FH studies of VTE are reviewed. FH in first-degree relatives (siblings and/or parents) is associated with a 2-3 times increased familial relative risk (FRR). However, the FRR is dependent on age, number of affected relatives, and presentation of VTE (provoked/unprovoked). Especially high familial risks are observed in individuals with two or more affected siblings (FFR> 50). However, the familial risk for recurrent VTE is much lower or non-significant. Moreover, FH of VTE appears mainly to be important for venous diseases (i. e. VTE and varicose veins). The familial associations with other diseases are weaker. In conclusion, FH of VTE is an important research tool and a clinically potential useful risk factor for VTE.
authors: Dr. Bengt Zöller, Center for Primary Health Care Research, CRC, Building 28, Floor 11, Jan Waldenströms gata 35, Skåne University Hospital, S-205 02 Malmö, Sweden, Tel: +46 40 391954, Fax: +46 40 391370, E-mail: bengt.zoller@med.lu.se.
authors: Bengt
authors: B
authors: Zöller
authors: Xinjun
authors: X
authors: Li
authors: Henrik
authors: H
authors: Ohlsson
authors: Jianguang
authors: J
authors: Ji
authors: Jan
authors: J
authors: Sundquist
authors: Kristina
authors: K
authors: Sundquist
mesh_terms: D000818:Animals; D005190:Family; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D036281:Genetic Research; D055106:Genome-Wide Association Study; D006801:Humans; D008487:Medical History Taking / Q000379:methods; D010375:Pedigree; D011486:Protein C / Q000235:genetics*; D012307:Risk Factors; D054556:Venous Thromboembolism / Q000453:epidemiology / Q000235:genetics*
chemical_list: D011486:Protein C
keywords: Familial thrombosis; epidemiological studies; pulmonary embolism; thrombophilia; venous thrombosis