INTERRELATION OF ALLELIC VARIANTS OF HEMOSTASIS SYSTEM GENES ON THE DEVELOPMENT AND COURSE OF LUPUS NEPHRITIS
https://doi.org/10.24884/1561-6274-2019-23-2-77-81
Abstract
THE AIM: to evaluate the effect of allelic variations in the hemostatic system genes on the development and course of lupus nephritis. PATIENTS AND METHODS. The study analyzed 100 patients with SLE Caucasians. 80 women and 20 men aged 16 to 73 years (mean age 37, ± 14 years). The duration of observation was for 73 patients over 5 years, for 18 – from 1 year to 5 years and for 9 – less than 1 year A rise in the level of creatinine in the blood above or equal to 2 mg / dl was considered a significant sign of impaired renal function. RESULTS. Among the patients included in the study, kidney damage was detected in 61 people (61%). In 33 of them (54.1%), a variant of renal pathology was observed according to the type of rapidly progressive lupus nephritis (BPVN). In patients with BH, mutations in the MTHFR (C677T) gene were statistically significantly more frequent (p = 0.033). The OR for the mutant genotype is 6.146 with 95% CI from 1.692 to 22.326. In patients with PWHD, mutations in the MTHFR (C677T) gene were statistically significantly more frequent (p = 0.031). The OR for the mutant genotype is 1.625 with 95% CI from 1.034 to 4.771. The five-year renal survival in carriers of the mutant allele of the MTHFR gene (C677T) is statistically significantly lower (72.8%) than in patients without this mutation (81.9%) (p = 0.027). Ten-year renal survival in carriers of the mutant allele of the MTHFR gene (C677T) is statistically significantly less (55.6%) than in patients without this mutation (70.5%) (p = 0.016). In patients with BH, mutations in the PAI-1 gene (4G / 5G 675) were statistically significantly more frequent (p = 0.046). OR for mutant genotype – 1.766 with 95% CI from 1.061 to 4.758. CONCLUSION. The mutant alleles of the MTHFR (C677T) and PAI-1 (4G / 5G 675) genes are likely to be associated with the development of BH. Polymorphism of the MTHFR gene (C677T) is associated with an unfavorable course of HH.
About the Authors
E. N. BorisovRussian Federation
Yevgeny N. Borisov, MD, Moscow State University named after MV Lomonosov, Medical Research and Education Center, general practitioner
L. V. Ivanitsky
Russian Federation
Associate Professor, MD, Moscow Oblast Scientific and Research Clinical Institute; MF Vladimirsky, Department of General Medical Practice (Family Medicine)
L. M. Samokhodskaya
Russian Federation
Associate Professor, MD, PhD, Moscow State University named after MV Lomonosov, Faculty of Fundamental Medicine, Laboratory of Genetic and Cellular Technologies of the Department of Biochemistry and Molecular Medicine, Head
T. N. Krasnova
Russian Federation
Associate Professor, MD, PhD, Moscow State University named after MV Lomonosov, Faculty of Fundamental Medicine, Department of Internal Medicine
E. P. Pavlikova
Russian Federation
Professor, MD, PhD, DMedSci, State University named after MV Lomonosov, Medical Research and Education Center, Department of Internal Diseases, Head
A. A. Kamalov
Russian Federation
Professor, MD, PhD, DMedSci, State University named after MV Lomonosov, Medical Research and Educational Center, Director, Academician of the Russian Academy of Sciences
References
1. Krasnova TN. Renal involvement in systemic lupus erythematosus: the present views of its pathogenesis and clinical manifestationsand the approaches to its treatment. Modern Rheumatology Journal 2008;2(3):18–21 (In Russ.) https://Doi.org/10.14412/1996- 7012-2008-483
2. Turrent-Carriles A, Herrera-Félix JP, Amigo MC. Renal Involvement in Antiphospholipid Syndrome. Front Immunol 2018; 9:1008. Doi: 10.3389/fimmu.2018.01008
3. Flores-Mendoza G, Sansón SP, Rodríguez-Castro S et al. Mechanisms of Tissue Injury in Lupus Nephritis. Trends Mol Med 2018;24(4):364–378. Doi: 10.1016/j.molmed.2018.02.003
4. Santilli F, Davì G, Patrono C. Homocysteine, methylene tetrahydrofolate reductase, folate status and atherothrombosis: A mechanistic and clinical perspective. Vascul Pharmacol 2016;78:1–9. Doi: 10.1016/j.vph.2015.06.009
5. Yuyun MF, Ng LL, Ng GA. Endothelial dysfunction, endothelial nitric oxide bioavailability, tetrahydrobiopterin, and 5-methyltetrahydrofolate in cardiovascular disease. Where are we with therapy? Microvasc Res 2018;119:7–12. Doi: 10.1016/j. mvr.2018.03.012
6. Liu Y, Cheng J, Guo X et al. The roles of PAI-1 gene polymorphisms in atherosclerotic diseases: A systematic review and metaanalysis involving 149,908 subjects. Gene 2018;673:167–173. Doi: 10.1016/j.gene.2018.06.040
7. Hamano K, Iwano M, Akai Y et al. Expression of glomerular plasminogen activator inhibitor type 1 in glomerulonephritis. Am J Kidney Dis 2002;39:695–705. Doi: 10.1053/ajkd.2002.31986
8. Liu Q, Imaizumi T, Kawaguchi S et al. Toll-like receptor 3 signaling contributes to regional neutrophil recruitment in cultured human glomerular endothelial cells. Nephron 2018;139:349–358
Review
For citations:
Borisov E.N., Ivanitsky L.V., Samokhodskaya L.M., Krasnova T.N., Pavlikova E.P., Kamalov A.A. INTERRELATION OF ALLELIC VARIANTS OF HEMOSTASIS SYSTEM GENES ON THE DEVELOPMENT AND COURSE OF LUPUS NEPHRITIS. Nephrology (Saint-Petersburg). 2019;23(2):77-81. (In Russ.) https://doi.org/10.24884/1561-6274-2019-23-2-77-81