[Prognostic value of allelic variants affecting the hemostatic system in the development of antiphospholipid syndrome and kidney lesion in patients with systemic lupus erythematosus].

AIM: To analyze the prognostic value of the polymorphisms of the thrombophilic genes: plasminogen activator inhibitor type 1 (PAI-1) (-675 4G/5G), factor XIII (FXIII) (G485T), fibrinogen (FBG) (G(-455)A), glycoprotein Ia (GPIa) (C807T), glycoprotein IIIa (GPIIIa) (T106C), and p22phox (C242T), as well as protein genes involved in the pathogenesis of endothelial dysfunction: subunits of p22phox NADH-oxidase (p22phox) (C242T), endothelial NO-synthase (eNOS) (G894T), and methylenetetrahydrofolate reductase (MTHFR) (C677T) for the development of antiphospholipid syndrome (APS) and a type of progressive lupous nephritis (LN) in patients with systemic lupus erythematosus (SLE). SUBJECTS AND METHODS: One hundred patients with SLE were examined and, according to the presence of clinical and laboratory signs of APS were divided into 2 groups: 1) 50 SLE patients with APS; 2) 50 SLE patients without APS who were matched for gender and age with Group 1 patients. The gene polymorphisms were analyzed using standard molecular genetic techniques. The frequency of clinical manifestations of APS and the type of progressive nephritis were analyzed in view of the genotypes of the patients.
RESULTS: Comparison of SLE patients with and without SLE revealed no statistically significant differences in the rates of alleles and genotypes. The patients with arterial and/or venous thrombosis in the presence of APS more frequently displayed a minor allele (T) and genotype (TT) of the p22phox gene than those with APS without thrombosis: T, 64.5 and 34%, respectively (p = 0.033); TT, 36 and 7% (p = 0.021); odds ratio (OR), 2.1 at 95% confidence interval (CI), 1.5 to 22.7). In the APS patients with livedo reticularis, the minor allele (T) and genotype (TT) of the eNOS gene were more common than in those without livedo: T, 33 and 10%, respectively (p = 0.019); TT, 15 and 0% (p = 0.031); OR, 2.49 at 95% CI, 1.2 to 28.9). In the patients with AFS and rapidly progressive LN (RPLN), the minor allele (T) and genotype (TT) of the MTHFR gene were much more frequently encountered: T, 46 and 27%, respectively (p = 0.038); TT, 30 and 0% (p = 0.033); OR, 3.1 at 95% CI, 1.4 to 32.7). The group of patients without APS exhibited no relationship between the examined polymorphisms and kidney lesion.
CONCLUSION: The mutant allele of the p22phox gene increases the risk of arterial and venous thrombosis; the polymorphism of the eNOS gene may be related to the higher incidence of impaired blood microcirculation in SLE concurrent with APS. The risk of RPLN in SLE patients with APS is probably associated with MTHFR gene mutation.