Low density lipoprotein receptor-related protein polymorphisms are not risk factors for venous thromboembolism

Abstract Low-density lipoprotein receptor-related protein is a receptor involved in factor VIII catabolism. In spite of elevated factor VIII coagulant activity levels being a well-established independent risk factor for venous thrombosis, the origin of this abnormality is unknown. In this study, we investigated the role of polymorphisms C220T (exon 22), A775P (exon 14) and D2080N (exon 39) in the gene coding for this receptor in 249 patients (100 males/149 female, mean age 36.5 SD:11 years) with venous thromboembolism and 366 controls (155 male/211 females, mean age 38 SD:11 years ) matched by age and gender. The polymorphisms C220T (CT OR: 0.9, 95%CI: 0.6–1.2; TT OR: 1.0, 95%CI: 0.6–1.5) and D2080N (OR: 0.8, 95%CI: 0.3–2.4) were not associated to thrombosis susceptibility while the polymorphism A775P was identified in neither patients or controls. D2080N polymorphism was associated with factor VIII and von Willebrand factor levels, in the control group. Heterozygous individuals (DN), compared with homozygotes individuals (DD), presented lower levels of factor VIII (mean difference: 42.3 IU/dL, 95%CI: 5.7–78.9) and von Willebrand factor (mean difference: 34.8 IU/dL, 95%CI: 4.9–64.6). In conclusion, we demonstrated an association between D2080N polymorphism with factor VIII and von Willebrand factor levels in Brazilian normal individuals. However, none of the three polymorphisms in low-density lipoprotein receptor related protein gene were related to venous thrombosis risk in these patients.