2658-6533Research Results in Biomedicine2658-653310.18413/2658-6533-2019-5-4-0-11833GeneticsThe role of interaction of polymorphic loci of the <em>FLG</em> gene in the development of chronic true eczema in womenThe role of interaction of polymorphic loci of the <em>FLG</em> gene in the development of chronic true eczema in womenBelyaevaTatyana M.BelyaevaTatyana M.tb201446@yandex.ru20195400

Background: Eczema is a multifactorial disease. Its development is determined by the polygenic basis and the action of inciting events of exogenous and endogenous nature. The aim of the study: To analyze the role of interaction of polymorphic loci of the filaggrin gene (FLG) in the development of chronic true eczema in women. Materials and methods: A sample of 446 women was formed for the study, including 233 patients with chronic true eczema and 213 women without the disease. All women involved in the study underwent the necessary clinical and clinical laboratory examination. Nine polymorphic loci of the filaggrin gene were genotyped. The SNP&times;SNP interactions involved in the formation of chronic true eczema were studied using the АРSampler software (using the Monte Carlo Markov chain method and Bayesian nonparametric statistics) and MDR (based on the MDR dimension reduction method). Results: The two-and three-locus models associated with disease formation include five polymorphic loci-rs61816761, rs4363385, rs77199844, rs471144, and rs558269137 of the FLG gene. Polymorphisms rs4363385 and rs77199844 are included in the largest number of models (6 models respectively). SNP&times;SNP interactions rs471144&times; rs77199844 and rs471144&times; rs4363385 determine&nbsp;-0.84% and -0.77% of trait entropy respectively. Polymorphic loci rs77199844 and rs471144 are localized in the region of DNA regulatory motives to 12 transcription factors, and polymorphism rs4363385 of the FLG gene is associated with the expression level of nine genes in the skin (SPRR1B, LCE3C, LCE1D, SPRR2D, SPRR2B, LCE3A, LCE1E, SPRR1A, SPRR3). Conclusion: Interactions of polymorphic loci of the FLG gene are associated with the development of chronic true eczema in women.

Background: Eczema is a multifactorial disease. Its development is determined by the polygenic basis and the action of inciting events of exogenous and endogenous nature. The aim of the study: To analyze the role of interaction of polymorphic loci of the filaggrin gene (FLG) in the development of chronic true eczema in women. Materials and methods: A sample of 446 women was formed for the study, including 233 patients with chronic true eczema and 213 women without the disease. All women involved in the study underwent the necessary clinical and clinical laboratory examination. Nine polymorphic loci of the filaggrin gene were genotyped. The SNP&times;SNP interactions involved in the formation of chronic true eczema were studied using the АРSampler software (using the Monte Carlo Markov chain method and Bayesian nonparametric statistics) and MDR (based on the MDR dimension reduction method). Results: The two-and three-locus models associated with disease formation include five polymorphic loci-rs61816761, rs4363385, rs77199844, rs471144, and rs558269137 of the FLG gene. Polymorphisms rs4363385 and rs77199844 are included in the largest number of models (6 models respectively). SNP&times;SNP interactions rs471144&times; rs77199844 and rs471144&times; rs4363385 determine&nbsp;-0.84% and -0.77% of trait entropy respectively. Polymorphic loci rs77199844 and rs471144 are localized in the region of DNA regulatory motives to 12 transcription factors, and polymorphism rs4363385 of the FLG gene is associated with the expression level of nine genes in the skin (SPRR1B, LCE3C, LCE1D, SPRR2D, SPRR2B, LCE3A, LCE1E, SPRR1A, SPRR3). Conclusion: Interactions of polymorphic loci of the FLG gene are associated with the development of chronic true eczema in women.

polymorphismassociationsSNP×SNP interactionschronic true eczemawomenFLGpolymorphismassociationsSNP×SNP interactionschronic true eczemawomenFLGСписок литературы[The Federal Clinical Guidelines. Dermatovenerology 2015: Diseases of the skin. Sexually transmitted infections]. 5th ed., revised. and add. Moscow: Business Express; 2016. Russian.Weidinger S, Novak N. Atopic dermatitis.&nbsp;Lancet.&nbsp;2016;387(10023):1109-1122. DOI: 10.1016/S0140-6736(15)00149-XBaurecht H, Hotze M, Brand S, et al. Genome-wide comparative analysis of atopic dermatitis and psoriasis gives insight into opposing genetic mechanisms. . 2015;96(1):104-120. DOI: 10.1016/j.ajhg.2014.12.004Yusupova LA, Yunusova EI, Garaeva ZSh, et al. [Modern features of the clinic, diagnostics and therapy of patients with eczema]. Lechashchiy vrach. 2018;6:85. Russian.Rerknimitr P, Otsuka A, Nakashima C, et al. The etiopathogenesis of atopic dermatitis: barrier disruption, immunological derangement, and pruritus. Inflamm Regen. 2017;37:14-15. DOI: 10.1186/s41232-017-0044-7Bin L, Leung DY. Genetic and epigenetic studies of atopic dermatitis. Allergy Asthma Clin Immunol. 2016;12:52. DOI: 10.1186/s13223-016-0158-5Marenholz I, Esparza-Gordillo J, R&uuml;schendorf F, et al. Meta-analysis identifies seven susceptibility loci involved in the atopic march. Nat Commun. 2015;6:8804. DOI: 10.1038/ncomms9804Paternoster L, Standl M, Chen CM, et al. Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis. Nat. Genet. 2012;44:187-192. DOI: 10.1038/ng.1017Sun LD, Xiao FL, Li Y, et al. Genome-wide association study identifies two new susceptibility loci for atopic dermatitis in the Chinese Han population. Nat. Genet. 2011;43:690-694. DOI: 10.1038/ng.851Esparza-Gordillo J, Weidinger S, Folster-Holst R, et al. A common variant on chromosome 11q13 is associated with atopic dermatitis. Nat. Genet. 2009;41:596-601. DOI: 10.1038/ng.347Hirota T, Takahashi A, Kubo M, et al. Genome-wide association study identifies eight new susceptibility loci for atopic dermatitis in the Japanese population. Nat. Genet. 2012;44:1222-1226. DOI: 10.1038/ng.2438Meng L, Wang L, Tang H, et al. Filaggrin Gene Mutation c.332 delA is associated with various clinical features of atopic dermatitis in the Chinese han population. PLoS One. 2014;9:e98235. DOI: 10.1371/journal.pone.0098235On HR, Lee SE, Kim SE, et al. Filaggrin Mutation in Korean Patients with Atopic Dermatitis. Yonsei Med J. 2017;58(2):395-400. DOI: 10.3349/ymj.2017.58.2.395Gimalova GF, Karunas AS, Fedorova YY, et al. [Replication analysis of genome wide studies of atopic dermatitis in the Republic of Bashkortostan]. Medical Genetics. 2016;15(4):25-28. Russian. DOI: https://doi.org/10.1234/XXXX-XXXX-2016-4-25-28Gimalova GF, Karunas AS, Fedorova YY, et al. The study of filaggrin gene mutations and copy number variation in atopic dermatitis patients from volga-ural region of Russia. GENE. 2016;591(1):85-89. DOI: https://doi.org/10.1016/j.gene.2016.06.054Sorokina IN, Rudykh NA, Bezmenova IN, et al. Population genetic characteristics and genetic epidemiological research of candidate genes associations with multifactorial diseases. Research Results in Biomedicine. 2018;4(4):20-30. Russian. DOI: 10.18413/2313-8955-2018-4-4-0-3Favorov AV, Andreewski TV, Sudomoina MA, et al. A Markov chain Monte Carlo technique for identification of combinations of allelic variants underlying complex diseases in humans. Genetics. 2005;171(4):2113-2121. DOI: 10.1534/genetics.105.048090Lvovs D, Favorova OO, Favorov AV. A Polygenic Approach to the Study of Polygenic Diseases. Acta Naturae. 2012;4(3):59-71.Ponomarenko IV, Reshetnikov EA, Polonikov AV, et al. [The polymorphic locus rs314276 of the LIN28B gene is associated with the age of menarche in women of the Central Black Earth Region of Russia]. Akusherstvo i ginekologiya. 2019;2:98-104. Russian. DOI: 10.18565 / aig.2019.2.98-104Ponomarenko IV, Polonikov AV, Churnosov MI. [Polymorphic LHCGR gene loci associated with the development of uterine fibroids]. Akusherstvo i ginekologiya. 2018;10:86-91. Russian. DOI: https://dx.doi.org/10.18565/aig.2018.10.86-91Malchenko EE, Nemchaninova OB, Maksimov VN. [Filaggrin role in development of chronic dermal diseases. Literature review]. Journal of Siberian Medical Sciences. 2015;(3):28. Russian.Levasheva SV, Etkina EI, Guryeva LL, et al. [Filaggrin gene mutations as a factor in dysregulation of the epidermal barrier in children]. Lechashchiy Vrach. 2016;1:24. Russian.Čepelak I, Dodig S, Pavić I. Filaggrin and atopic march.&nbsp;. 2019;29(2):020501. DOI: 10.11613/BM.2019.020501Brown SJ, McLean WH. One remarkable molecule: filaggrin.&nbsp;. 2012;132(3 Pt 2):751-762. DOI: 10.1038/jid.2011.393Čepelak I, Dodig S, Filipović-Grčić J. Filaggrin &ndash; multifunctional protein. Acta Med Croatica. 2016;70:125-30.Ferreira MA, Vonk JM, Baurecht H, et al. Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology. . 2017;49(12):1752-1757. DOI: 10.1038/ng.3985Ferreira MAR, Mathur R, Vonk JM, et al. Genetic Architectures of Childhood- and Adult-Onset Asthma Are Partly Distinct. Am J Hum Genet. 2019;104(4):665-684. DOI: 10.1016/j.ajhg.2019.02.022