The genetics of venous thromboembolism: a systematic review of thrombophilia families

Genetic risk factors are important for the occurrence and prognosis of venous thromboembolism (VTE). The studies of thrombophilia families are important for dissecting the genetic background of the thrombotic disease. We conducted the systematic review of all published family-based studies on VTE genetics across all racial groups through PubMed and Embase prior to 13th April 2020. This systematic review of 287 families (including 225 Caucasian families, 52 East Asian families, and families of other ethnicities) revealed a total of 21 different genes; the five most reported mutated genes were F5 (88/287, 30.7%), SERPINC1 (67/287, 23.3%), PROC (65/287, 22.6%), F2 (40/287, 13.9%) and PROS1 (48/287, 16.7%). For Caucasian families, F5 mutations were most frequently reported at 37.8% (85/225), while PROS1 mutations were most frequently reported, at 40.4% (21/52), for East Asian families (Chinese, Japanese and Korean). Factor V Leiden was reported more frequently in Caucasians than in East Asians. Missense mutations were reported frequently in the SERPINC1, PROC and PROS1 genes. In conclusion, our study found the most likely mutated genes associated with VTE among different ethnic groups and provided indications for VTE genetic testing and research in the future.