FRI0400 Prognostic Role of Allelic Variations of Genes Affecting Haemostasis in the Development of Antiphospholipid Syndrome and Renal Damage in Patients with Systemic Lupus Erythematosus

Abstract

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 ...

Decisive evidence corroborates a null relationship between MTHFR C677T and chronic kidney disease

“…Moreover, 6 articles were manually added from previous meta-analyses. Excluded were: 61 repeated articles, 37 non-case–control studies, 56 articles without CKD, 11 articles focused on kidney transplantation patients, 8 articles for hereditary kidney disease, [ 45 – 60 ] 5 articles that did not provide complete genotype information, [ 22 , 61 – 64 ] 10 articles without MTHFR C677T, [ 65 – 74 ] 1 familial study, [ 75 ] 2 articles on minors, [ 76 , 77 ] 3 articles for auto-immune diseases, [ 78 – 80 ] 3 articles covering non-Asian and non-Caucasians, [ 81 – 83 ] 1 article with an incorrect definition of a control group, [ 84 ] 1 article using a duplicated population, [ 18 ] and 6 non-English articles. [ 85 – 90 ] Finally, 33 papers were included for meta-analysis.…”

<p>Association of Plasminogen Activator Inhibitor 1 (PAI-1) 4G/5G Polymorphism and Susceptibility to SLE in Egyptian Children and Adolescents: A Multicenter Study</p>

“…30 In contrast, previous studies did not identify any association between the PAI-1 4G/5G polymorphism and lupus susceptibility or its clinical expression in Russian, Bulgarian, Spanish, and Argentinean SLE cohorts with adult-onset disease. [31][32][33][34] Similarly, a recent meta-analysis of nine studies demonstrated that the PAI-1 4G/5G polymorphism did not increase the risk of SLE or LN among Asian and European populations, although they reported significant up-regulation of circulating PAI-1 activity in multi-ethnic cohorts with adult-onset SLE. 11 Ethnic background or gene-environmental interplay as well as differences in cohort size and studied age group may partly explain these discrepancies between our study and previously published data.…”

Association of NCF2, NCF4, and CYBA Gene Polymorphisms with Rheumatoid Arthritis in a Chinese Population

“…Apart from NCF1 , several single nucleotide polymorphisms (SNPs) in NCF2 , NCF4 , and CYBA genes were reported to be associated with autoimmune diseases [ 15 – 17 ]. The results by Olsson et al indicated that the NCF4 rs729749 variant was involved in the development of RA in a Swedish cohort [ 16 ].…”