Erytrocyte-related phenotypes and genetic susceptibility to thrombosis

Venous thromboembolism (VTE) is a common disease that involves the interaction of genetic and environmental risk factors. Previous studies have estimated a heritability of approximately 60% for the risk of VTE. Using variance analysis, intermediate phenotypes related to thrombosis have been used to identify genetic risk factors. Erythrocyte intermediate phenotypes are good candidates for VTE risk factors. We investigated the relationship of erythrocyte-related phenotypes with the risk of VTE. Our study used the Genetic Analysis of Idiopathic Thrombophilia 2 (GAIT2 Project) sample, which consisted of 35 extended pedigrees (including a total of 935 individuals). The sample had 120 subjects with thromboembolism (86 with VTE, 47 with arterial thrombosis and 13 with both). The following risk factors were evaluated: Red blood cell parameters, reticulocytes, serum iron, total iron binding capacity, serum ferritin, serum transferrin receptor (STFR), and haptoglobin. Using the variance component method, heritability (h2) and the phenotypic, genetic and environmental correlations with VTE were estimated. The h2 of VTE was 0.67. Most erythrocyte parameters showed significantly high h2. In addition, VTE was genetically correlated with: hematocrit (ρG = 0.52, p = 0.01), red blood cell distribution width (RDW) (ρG = 0.28, p = 0.05), immature reticulocyte fraction (IRF) (ρG = 0.45, p = 0.008), transferrin saturation index (ρG = − 0.7, p = 0.05), and STFR (ρG = 0.4, p = 0.006). In conclusion, a genetic relationship between erythrocyte intermediate phenotypes and VTE was demonstrated. Also, we identified 5 phenotypes as risk factors. These phenotypes are useful in the search for genes that affect VTE.