ARTHRITIS & RHEUMATISM Vol. 48, No. 2, February 2003, pp 471–474 DOI 10.1002/art.10771 © 2003, American College of Rheumatology Valine/Valine Genotype at Position 247 of the  2 -Glycoprotein I Gene in Mexican Patients With Primary Antiphospholipid Syndrome Association With Anti– 2 -Glycoprotein I Antibodies G. Aleph Prieto, Antonio R. Cabral, Martı ´n Zapata-Zun ˜iga, Abraham J. Simo ´n, Antonio R. Villa, Donato Alarco ´n-Segovia, and Javier Cabiedes Objective. To determine the polymorphism at position 247 of the  2 -glycoprotein I ( 2 GPI) gene in Mexican patients with antiphospholipid syndrome (APS) and to compare these data in patients with or without antibodies to  2 GPI and with the clinical man- ifestations of APS. Methods. We studied 39 patients with primary APS and compared them with 106 clinically healthy subjects. Polymorphism was determined by polymerase chain reaction–restriction fragment length polymor- phism. The presence of “true” anticardiolipin (aCL) antibodies,  2 GPI-dependent aCL antibodies (IgG and IgM), and phospholipid-free anti- 2 GPI antibodies (IgG isotype) were detected by enzyme-linked immu- nosorbent assay (ELISA) utilizing nonirradiated ELISA plates. Clinical manifestations associated with anti- phospholipid antibodies were also evaluated. Results. We found no significant differences in the genotype expression between the control group and the primary APS patients (13% with VV, 52% with VL, and 35% with LL versus 23% with VV, 51% with VL, and 26% with LL, respectively). In contrast, anti- 2 GPI– positive patients had significantly higher frequencies of the VV genotype and V allele expression than the control subjects and the anti- 2 GPI–negative patients. These genotype and allele frequencies were also significantly higher in patients with arterial thrombosis than in patients without it. Anti- 2 GPI–negative patients with- out arterial thrombosis did not express the VV genotype. We found no differences in the Val/Leu 247 polymorphism of the  2 GPI gene in primary APS patients with or without “true” aCL antibodies or in primary APS patients with or without  2 GPI-dependent aCL antibodies. Conclusion. Our results suggest that the VV genotype at position 247 of the  2 GPI gene may play a role in the generation of anti- 2 GPI antibodies and perhaps in the expression of arterial thrombosis in primary APS. The antiphospholipid syndrome (APS) is a well- defined clinical entity characterized by serum antiphos- pholipid antibodies, arterial and/or recurrent venous thrombosis, recurrent fetal loss, livedo reticularis, thrombocytopenia, hemolytic anemia, and neurologic disorders (1). In 1990, three groups of investigators independently found that anticardiolipin (aCL) antibod- ies from patients with APS required the presence of  2 -glycoprotein I ( 2 GPI) for their detection in vitro (2–4). This finding suggested that the aCL antibodies recognized epitopes on the phospholipid– 2 GPI com- plex or, alternatively, that the aCL antibodies recognized cryptic epitopes in CL and/or  2 GPI proper (2,3). Variations in  2 GPI among individuals of the Supported by grants from the Consejo Nacional de Ciencia y Tecnologı ´a, Mexico. Dr. Cabral is a recipient of the Beatriz Va ´zquez Sa ´mano Career Investigator award for research on antiphospholipid cofactor syndromes. Dr. Cabiedes is a recipient of the Fundacio ´n Teleto ´n Me ´xico award for research on antiphospholipid cofactor antibodies and related themes. G. Aleph Prieto, BSc, Antonio R. Cabral, MD, Martı ´n Zapata-Zun ˜iga, MD, Abraham J. Simo ´n, MD, Antonio R. Villa, MD, Donato Alarco ´n-Segovia, MD, PhD, Javier Cabiedes, PhD: Instituto Nacional de Ciencias Me ´dicas y Nutricio ´n Salvador Zubira ´n, Mexico City, Mexico. Address correspondence and reprint requests to Javier Ca- biedes, PhD, Instituto Nacional de Ciencias Me ´dicas y Nutricio ´n Salvador Zubira ´n, Vasco de Quiroga 15, Mexico DF 14000, Mexico. E-mail: jcabiedesc@sni.conacyt.mx. Submitted for publication July 17, 2002; accepted in revised form October 16, 2002. 471