Genetic risk factors of thrombosis in the antiphospholipid syndrome

Abstract

SummaryThe possibility of a genetic predisposition to develop antiphospholipid syndrome (APS) and to produce anticardiolipin antibodies and lupus anticoagulant has been addressed by family studies and population studies. Various studies suggest a familial occurrence of anticardiolipin antibodies and lupus anticoagulant, with or without clinical evidence of APS. This familial tendency could be genetically determined. Multiple human leucocyte antigen-DR or -DQ associations with antiphospholipid antibodies have been described. Genetic studies of a representative antigen, beta2-glycoprotein-I (b 2 GPI), have been carried-out and a particular valine 247 / leucine polymorphism could be a genetic risk for presenting anti-b 2 GPI antibodies and APS. Many other thrombosisrelated genetic factors have been investigated in APS, but no additional risk for thrombosis has been indicated in affected patients. Although the mechanisms and pathophysiology of thrombosis in APS are highly heterogeneous and multifactorial, different genes and acquired factors seem to be involved. In this review, we will focus on those genetic variants that could contribute to the development of thrombosis in APS.

Challenges in the Diagnosis of the Antiphospholipid Syndrome

“…These additional risk factors include age, the established risk factors for cardiovascular disease, inherited thrombophilias (such as factor V Leiden or prothrombin mutation G20210A), use of oral contraceptives, nephrotic syndrome, malignancy, immobilization, and surgery (22 ). Possible genetic predisposition for developing APS and producing APAs has been addressed in family and population studies (41 ). Associations of APS and APAs have been described with human leukocyte antigen-DR and -DQ, as well as with polymorphisms in the ␤2GPI antigen, the genes encoding for platelet glycoproteins, the signaling pathways for proinflammatory mediators, and genetic defects of the immune system (e.g., IgA or complement) (42 ).…”

Familial antiphospholipid syndrome presenting as bivessel arterial occlusion in a 17-year-old girl

“…Everything considered, mechanisms and pathophysiology of thrombosis in APS are highly heterogeneous and multifactorial, and that's why different genes and acquired factors seem to be involved [10], [7].…”

“…Another representative antigen, β 2 -glycoprotein-I (β 2 -GPI), expresses a valine(247)/leucine polymorphism which could be another genetic risk for presenting anti-β 2 -GPI antibodies and APS [10], [11].…”

Pathogenic and Therapeutic Role of Vitamin D in Antiphospholipid Syndrome Patients

“…Although APS represents acquired, autoimmune condition, its pathophysiology and, especially pathophysiology of thrombosis in APS is highly heterogeneous, involving different genes and acquired factors [86], VitD insufficiency/deficiency being among them.…”