Lourdes Ortiz-Fernández1, Amr H Sawalha2,3,4. 1. Division of Rheumatology, Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh, 7123 Rangos Research Center, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA. 2. Division of Rheumatology, Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh, 7123 Rangos Research Center, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA. asawalha@pitt.edu. 3. Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. asawalha@pitt.edu. 4. Lupus Center of Excellence, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. asawalha@pitt.edu.
Abstract
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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.
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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.
Authors: María Elena Rodríguez-García; Francisco Javier Cotrina-Vinagre; Marcello Bellusci; Ana Martínez de Aragón; Laura Hernández-Sánchez; Patricia Carnicero-Rodríguez; Elena Martín-Hernández; Francisco Martínez-Azorín Journal: Eur J Hum Genet Date: 2019-05-03 Impact factor: 4.246
Authors: R Cervera; R Serrano; G J Pons-Estel; L Ceberio-Hualde; Y Shoenfeld; E de Ramón; V Buonaiuto; S Jacobsen; M M Zeher; T Tarr; A Tincani; M Taglietti; G Theodossiades; E Nomikou; M Galeazzi; F Bellisai; P L Meroni; R H W M Derksen; P G D de Groot; M Baleva; M Mosca; S Bombardieri; F Houssiau; J-C Gris; I Quéré; E Hachulla; C Vasconcelos; A Fernández-Nebro; M Haro; Z Amoura; M Miyara; M Tektonidou; G Espinosa; M L Bertolaccini; M A Khamashta Journal: Ann Rheum Dis Date: 2014-01-24 Impact factor: 19.103
Authors: S Jiménez; D Tàssies; G Espinosa; A García-Criado; J Plaza; J Monteagudo; R Cervera; J C Reverter Journal: Ann Rheum Dis Date: 2007-08-29 Impact factor: 19.103