Valine/valine genotype at position 247 of the β₂‐glycoprotein I gene in Mexican patients with primary antiphospholipid syndrome: Association with anti–β₂‐glycoprotein I antibodies

Abstract

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 manifestations 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 polymorphism. 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 immunosorbent assay (ELISA) utilizing nonirradiated ELISA plates. Clinical manifestations associated with antiphospholipid 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 GPIpositive 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 without 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.

Beta2-glycoprotein I gene polymorphisms Val247Leu and Trp316Ser in Spanish patients with primary antiphospholipid syndrome

“…PCR products were separated on a 2% agarose gel. Enzyme digestion was performed with I (for Val247Leu; New England Biolabs, Spain) and BstB I (for Trp316Ser) (New England Biolabs, Spain), as previously described [12].…”

“…While studies in Asian [7,11] and American Hispanic [12][13][14] populations have identified clinical and serological associations between APS and b2GPI gene polymorphisms, other studies, mainly in Caucasian populations, have found no such relationship [7,[15][16][17]. The current study evaluated the presence of polymorphisms Val247Leu and Trp316Ser in a Spanish population of APS patients and healthy controls and the possible correlation with the development of anti-b2GPI antibodies and other aPL and associated clinical manifestations.…”

Polimorfismo Val247Leu do gene β2-glicoproteína 1 pode justificar a gênese de anticorpos antiβ2GP1 e síndrome do anticorpo antifosfolípide na hanseníase multibacilar

“…22 A troca do aminoácido Leu pela Val (códon 247), no V domínio da β 2 GP1, pode ocasionar modificação estrutural na proteína, ocasionando a produção de anticorpos antiβ 2 GP1, presentes na SAF, 23 e os indivíduos que apresentam homozigose Val247Val possuem maior risco de desenvolver SAF. 24,25 Neste estudo avaliou-se o polimorfismo genéti-co, localizado no códon 247 do exon 7 do gene da β 2 GP1 em amostra populacional brasileira composta por indivíduos hansênicos e saudáveis. Houve maior prevalência do genótipo Val/Val no grupo de hansêni-cos, em relação à do grupo controle.…”

“…Todos os pacientes MB com FTE apresentaram heterozigose ou homozigose (Val/Val), corroborando estudos que atribuem FTE e SAF ao polimorfismo Val247Leu. 13,24,25 Alguns estudos têm relacionado a presença desse polimorfismo com AAF em pacientes com SAF, porém os resultados são controversos. Paloma et al [24][25][26][27] Na hanseníase MB, há descrição da presença de AAF, porém a ocorrência da associação com SAF é rara.…”

“…13,24,25 Alguns estudos têm relacionado a presença desse polimorfismo com AAF em pacientes com SAF, porém os resultados são controversos. Paloma et al [24][25][26][27] Na hanseníase MB, há descrição da presença de AAF, porém a ocorrência da associação com SAF é rara. 13 Até o momento não há relato na literatura da descrição desse polimorfismo com AAF na hanseníase.…”