Genetics of Antiphospholipid Syndrome

Antiphospholipid syndrome (APS) is a rare heterogenous disorder associated with the presence of antiphospholipid antibodies and can present in a wide variety of clinical manifestations including thrombosis and pregnancy complications. Although the etiology of APS remains poorly understood, there is strong support for considering APS as a complex genetic disease in which multiple genetic risk factors, in conjunction with environmental factors, affect its onset, progression, and severity. Here, we provide a comprehensive review of the current knowledge of the genetic basis of APS, which remains in its infancy.

Most genetic studies to date in APS were performed in small cohorts of patients. As a result, only few genetic associations reported are convincing. Several reports suggested genetic associations with HLA class II alleles in APS, and only two genetic loci outside of the HLA region (STAT4 and C1D) reached the threshold for genome-wide level of significance (P < 5 × 10^-8). In this review, we also shed light on the genetic differences among the diverse clinical subsets of APS and briefly discuss the role that DNA methylation changes might play in the pathophysiology of this disease. The genetic basis of APS remains poorly characterized. Larger collaborative multicenter studies using well-characterized patients are needed to comprehensively understand the role of genetic susceptibility in APS.