IL1b T-31C and VEGFРђ C+936T SNPs may be used as prognostic markers of rheumatoid arthritis treatment inefficiency

Poster (download) Vitaly Omelchenko1, Elena Letyagina2, Alla Shevchenko3, Yuliya Kurochkina4, Anna Akimova5, Maxim Korolev61Research Institute of Clinical and Experimental LymСЂhology – Branch of the Institute of Cytology and Genetics, v.o.omelchenko@gmail.com2Research Institute of Clinical and Experimental LymСЂhology – Branch of the Institute of Cytology and Genetics, elena_letyagina@list.ru3Research Institute of Clinical and Experimental LymСЂhology – Branch of the Institute of Cytology and Genetics, shalla64@mail.ru4Research Institute of Clinical and Experimental LymСЂhology – Branch of the Institute of Cytology and Genetics, juli_k@bk.ru5Research Institute of Clinical and Experimental LymСЂhology – Branch of the Institute of Cytology and Genetics, calor844@gmail.com6Research Institute of Clinical and Experimental LymСЂhology – Branch of the Institute of Cytology and Genetics, kormax@bk.ru Objectives: The aim of our study was to analyze the association between some SNPs and treatment of rheumatoid arthritis with biological drugs. Patients and methods: We studied 368 Russian patients with rheumatoid arthritis. All of them were treated in accordance with the standard recommendations. Fifty seven patient received biological disease-modifying antirheumatic drugs. Single nucleotide polymorphisms (TNFО± C-863A, TNFО± G-308A, TNFО± G-238A, IL1ОІ T-31РЎ, IL4 РЎ-590T, IL6 G-174C, IL10 A-1082G, IL10 РЎ-592Рђ, VEGFA C+936T, VEGFA C-2578A) were determined by restriction fragment length polymorphism analysis of PCR-amplified fragments (PCR-RFLP) or RT-PCR. Results: The IL1ОІ T-31C and VEGFA C+936T SNPs were association with bDMARDs treatment. Homozygotes IL1b -31CC and VEGFРђ +936 CC were more frequently in bDMARDs group compare with patients without bDMARDs (28.1% vs 17.1%, p=0.044 and 80.4% vs 66.6%, p=0.041). Other polymorphisms didn’t demonstrate any significant differences. Conclusions: Our data suggest, that IL1ОІ T-31C and VEGFA C+936T SNPs can be used as part of a comprehensive assessment of the prognosis of the treatment effectiveness.

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Candidate SNP markers of rheumatoid arthritis changing the affinity of TATA-binding protein for the human gene promoters expo disruptive selection of immunoactivative and immunosuppressive genenets that provoke and prevent this disorder, respectively, as if it could be a self-domestication syndrome

Poster (download) Natalya Klimova1, Dmitry Oshchepkov2, Irina Chadaeva3, Mikhail Ponomarenko4, Evgeniya Oshchepkova5, academician Vladimir Kozlov61Molecular Genetics Department, Institute of Cytology and Genetics, ICG SB RAS, Novosibirsk, Russia, klimova@bionet.nsc.ru2Systems Biology Department, Institute of Cytology and Genetics, ICG SB RAS, Novosibirsk, Russia, diman@bionet.nsc.ru3Systems Biology Department, Institute of Cytology and Genetics, ICG SB RAS, Novosibirsk, Russia, ichadaeva@bionet.nsc.ru4Systems Biology Department, Institute of Cytology and Genetics, ICG SB RAS, Novosibirsk, Russia, pon@bionen.nsc.ru5Systems Biology Department, Institute of Cytology and Genetics, ICG SB RAS, Novosibirsk, Russia, nzhenia@bionet.nsc.ru6Research Institute of Fundamental and Clinical Immunology, RIFCI SB RAS, Novosibirsk, Russia, niiki01@online.nsk.su Here we conducted a computational genome-wide study of the all known single-nucleotide polymorphism (SNP) of 70 bp proximal promoters of 67 human rheumatoid arthritis (RA)-related genes that displayed disruptive natural selections of immunoactivative or immunosuppressive genes raising or reducing risks of RA, respectively, as if it maybe a domestication syndrome. That is why, we confirmed it in vivo using the genome-wide transcriptome profiling (RNA-seq assay) of the differentially expressed genes (DEGs) within hypothalamus of adult male rats (Rattus norvegicus) of two unique outbred lines bred in aggressiveness and tameness as an animal model of human diseases (statistical significance padj < 0.025 at Pearson\’s П‡2 criterion with Bonferroni\’s correction).

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