Background Secondary Antiphospholipid Syndrome (APS) can develop in 20-30% of patients with Systemic Lupus Erythematosus (SLE). Renal damage in the form of Lupus nephritis (LN) develops in 50-70% of SLE patients. Thrombotic microangiopathy (TMA) in patients with APS adds to the renal damage. It is known that risk of thrombotic complications increases when defects in genes affecting haemostasis are present.
Objectives To study prognostic role of the PAI-1 (4G/5G 675), Factor XIII (G485T), FBG G (-455)A), GPIa (C807T), GPIIIa (T196C), p22phox (C242T), eNOS (G894T), MTHFR (C677T) thrombophilia genes polymorphisms in development of clinical and laboratory manifestations of APS and LN in patients with SLE and APS.
Methods The study involved 100 SLE patients of Caucasian race, 80 (80%) of which were females and 20 (20%) were males in the age from 16 to 73 years. Polymorphisms were analysed with molecular genetic analysis methods. SLE was diagnosed according to American College of Rheumatology's criteria. APS was diagnosed using clinical and laboratory criteria developed in 2006. Patients groups (comparable in age and sex) were as follows: first group of 50 patients with SLE and APS, and second group of 50 patients with SLE without APS. Frequency of allelic variations of studied genes were compared between groups. Analysis of frequency of clinical manifestations of APS and LN was performed taking patients' genotypes into account.
Results When comparing patients with SLE with APS and SLE without APS statistically significant differences were not observed. Patients with APS-associated arterial and/or venous thromboses more frequently have minor allele (T) and genotype (TT) p22phox (C242T) compared to patients with APS without thromboses; T: 64.5% vs 34% (p=0.033), TT: 36% vs 7% (p=0.021, OR=2.1 (95% confidence interval (CI) 1.5-22.7). Patients with livedo reticularis and APS more frequently had minor allele (T) and genotype (TT) eNOS (G894T) compared to patients without livedo; T: 33% vs 10% (p=0.019), TT: 15% vs 0% (p=0.031, OR=2.49 (95% CI 1.2-28.9). Patients with APS and rapidly progressive lupus nephritis (RPLN) considerably more frequently had minor allele (T) and genotype (TT) MTHFR (C677T); T: 45% vs 27% (p=0.038), TT: 30% vs 0% (p=0.033, OR=3.1 (95% CI 1.4-32.7). In the group of patients without APS no correlation between studied polymorphisms and renal damage was found.
Conclusions Having mutant allele of p22phox (C242T) subunit of NADPH-oxidase increases risk of developing arterial and venous thromboses in patients with SLE and APS. eNOS (G894T) gene polymorphism is associated with higher frequency of blood microcirculation disorders in organs and tissues of patients with SLE and APS. RPLN development risk in patients with SLE is probably related to mutation in MTHFR gene (C677T). Allelic contribution of PAI-1 (4G/5G 675), Factor XIII (G485T), FBG (G (-455)A), GPIa (C807T) and GPIIIa (T196C) is less pronounced in development of thrombotic complications within SLE with APS, probably because of existence of more important thrombosis risk factors in this systemic disease.
Disclosure of Interest None declared