title: Val/Leu247 and Trp/Ser316 polymorphisms in beta 2 glycoprotein I and their association with thrombosis in unselected Chilean patients.
abstract: It is known that polymorphisms of beta (2)-glycoprotein I (beta (2)GPI) in exon 7 affect interaction between the phospholipid binding site and the antibodies, and that other polymorphisms in exon 8 increase the generation of antibodies. In this study, we analyzed genetic polymorphisms of beta (2)GPI in unselected Chilean patients to determine the prevalence of beta (2)GPI polymorphisms in the phospholipid domain in patients with venous and arterial thrombosis and the clinical correlation with thromboembolic complications. This study comprised 149 patients with venous and arterial thrombosis (62 with venous thrombosis and 87 with arterial thrombosis) and 160 healthy controls with no previous history of thrombosis. Polymorphisms of exons 7 and 8 of beta (2)GPI, which encode for its fifth domain, were determined by PCR-RFLP. The presence of aPL or anti-beta (2)GPI in the patients was detected by ELISA. Anti-beta (2)GPI were present in 8/149 patients (5.4%); of these, five had aCL antibodies of low titer. The allele containing Val/Leu(247) and Trp/Ser(316) was significantly more frequent in patients with thrombosis than in the control group (OR=3.1, CI 1.6-6.0, p=0.0003; OR=2.9, CI 1.1-8.6, p=0.027, respectively). These polymorphisms did not correlate with aPL or anti-beta (2)GPI but significant differences were observed with venous thrombosis (p=<0.0001) and arterial thrombosis (p=0.026). In conclusion, the beta (2)GPI polymorphisms Val/Leu(247) and Trp/Ser(316) are not related to the presence of anti-beta (2)GPI antibodies in unselected Chilean patients with venous and arterial thrombosis, but they are significantly associated with venous and arterial thrombosis.
authors.affiliation: Department of Clinical Biochemistry and Immunohematology, Faculty of Health Sciences, Universidad de Talca, P.O. Box 747, Talca, Chile. ipalomo@utalca.cl
authors.forename: Iván
authors.initials: I
authors.lastname: Palomo
authors.forename: Jaime
authors.initials: J
authors.lastname: Pereira
authors.forename: Marcelo
authors.initials: M
authors.lastname: Alarcón
authors.forename: Marcela
authors.initials: M
authors.lastname: Vásquez
authors.forename: Carmen
authors.initials: C
authors.lastname: Pinochet
authors.forename: Fernando
authors.initials: F
authors.lastname: Poblete
authors.forename: Evelyn
authors.initials: E
authors.lastname: Mendez
authors.forename: Jeannette
authors.initials: J
authors.lastname: Sandoval
authors.forename: Rolando
authors.initials: R
authors.lastname: Vidal
authors.forename: Silvia
authors.initials: S
authors.lastname: Pierangeli
mesh_terms: D000328:Adult; D017152:Antibodies, Antiphospholipid / Q000097:blood; D002677:Chile; D003328:Coronary Thrombosis / Q000208:ethnology / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D020521:Stroke / Q000235:genetics*; D019851:Thrombophilia / Q000235:genetics* / Q000276:immunology; D020246:Venous Thrombosis / Q000208:ethnology / Q000235:genetics*; D053482:beta 2-Glycoprotein I / Q000235:genetics* / Q000276:immunology
chemical_list: D017152:Antibodies, Antiphospholipid; D053482:beta 2-Glycoprotein I