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

Abstract

The significance of beta2-glycoprotein I (β2GPI) polymorphisms in the production of anti-β2GPI and other antiphospholipid autoantibodies (aPL) and in the pathogenesis of primary antiphospholipid syndrome (PAPS) is not well understood. We performed a study comparing the distribution of polymorphisms at codons 247 (Val247Leu) and 316 (Trp316Ser) of the β2GPI gene in a Caucasian Spanish population of PAPS patients and healthy controls, and then making correlations with the development of anti-β2GPI antibodies and other aPL and associated clinical manifestations. A total of 57 PAPS patients and 100 control subjects were included. In the analysis of Val247Leu polymorphism, alleles (V and L) and genotypes (V/V, V/L, L/L) were similarly distributed in PAPS patients and controls (P = 0.66 and P = 0.22, respectively). Regarding Trp316Ser polymorphism, we found a higher percentage of patients with respect to controls expressing S allele (11.4 vs. 5%, P = 0.02) and T/S genotype (22.8 vs. 10%, P = 0.02). However, when we compared T/T and T/S genotypes in PAPS patients, we found no differences regarding generation of anti-β2GPI, other aPL and clinical manifestations favoring any genotype. Our findings suggest that among Spanish Caucasians, polymorphisms at codon 247 (Val247Leu) do not seem to influence PAPS pathogenesis. On the contrary, polymorphisms at codon 316 (Trp316Ser), by means of an increased S allele and T/S genotype presence in Spanish Caucasian patients, might play a role in the pathogenic development of PAPS, although mechanism would not involve an increased production of anti-β2GPI and other aPL.

Val/Leu247 polymorphism of β2‐glycoprotein I and thrombosis in Chinese patients with SLE

“…Ysuda et al [5] also showed an increased frequency of V/V genotype among Japanese patients. In contrast, Pardos-Gea et al [15] reported that the genotype and allele frequencies of the b 2 GPI gene were not correlated with thrombosis.…”

“…In contrast, Pardos‐Gea et al . reported that the genotype and allele frequencies of the β 2 GPI gene were not correlated with thrombosis.…”

What is the Genetics of Antiphospholipid Antibodies/Syndrome?

“…In unselected Chilean patients, it was associated with venous and arterial thrombosis but not aβ 2 GPI [ 41 ] . In contrast, 3 studies did not fi nd a relationship between the Val/Leu 247 polymorphism and aβ 2 GPI and/or primary APS in Caucasian patients [ 40 ] , Polish Caucasian patients [ 46 ] , or Spanish Caucasian patients [ 47 ] . Comparisons of cross-sectional autoantibody measures with genetic variants may be diffi cult to interpret since there remains poor standardization of these assays and critical autoantibodies may not be detectable on a single sample taken once in the lifetime of a patient.…”

New Biomarkers for Atherothrombosis in Antiphospholipid Syndrome: Genomics and Epigenetics Approaches

“…This genotype frequency is elevated in APS patients, especially in those with thrombosis (50). These studies pointed out to selectin-PSGL1 system genetic variations as determinant of thrombotic predisposition in patients with APS.Two single nucleotide variations in β2-Glycoprotein gene have been found increased in APS: G796T and G1004C, more known by the changes in aminoacidic sequence; Val247Leu and Trp316Ser, respectively (58, 59). The presence of these SNVs may lead to a conformational change in β2GPI that affects the exposure of potential epitopes, which in turn may favor thrombosis.…”

“…However, the relationship with either arterial or venous thrombosis is not clear (59). In the same way, the presence of Trp316Ser SNV may increase the risk of APS, but there is no relationship with thrombosis or antibodies production (58). Thus, further studies might be required to evaluate the pathogenic link between these SNVs and thrombosis in APS.Pierangeli et al evaluated the prevalence of two SNVs in Toll-like receptor 4 (TLR4) gene in 100 APS patients: A896G and C1196T.…”