Gene–Gene and Gene-Sex Epistatic Interactions of MiR146a, IRF5, IKZF1, ETS1 and IL21 in Systemic Lupus ErythematosusReportar como inadecuado




Gene–Gene and Gene-Sex Epistatic Interactions of MiR146a, IRF5, IKZF1, ETS1 and IL21 in Systemic Lupus Erythematosus - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Several confirmed genetic susceptibility loci involved in the interferon signaling and Th17-B cell response for SLE in Chinese Han populations have been described. Available data also indicate that sex-specific genetic differences contribute to SLE susceptibility. The aim of this study was to test for gene–gene-gene-sex epistasis interactions in these known lupus susceptibility loci. Six single-nucleotide polymorphisms SNPs in MiR146a, IRF5, IKZF1, ETS1 and IL21 were genotyped by Sequenom MassArray system. A total of 1,825 subjects 858 SLE patients and 967 controls were included in the final analysis. Epistasis was tested by additive model, multiplicative model and multifactor dimensionality reduction MDR method. Additive interaction analysis revealed interactions between IRF5 and IKZF1 OR 2.26, 95% CI 1.48–3.44 P = 1.21×104. A similar tendency was also observed between IL21 and ETS1 by parametric methods. In addition, multiple high dimensional gene-gene or gene-sex interactions three-and four-way were identified by MDR analysis. Our study identified novel gene–gene-gene-sex interactions in lupus. Furthermore, these findings highlight sex, interferon pathway, and Th17-B cells as important contributors to the pathogenesis of SLE.



Autor: Rui-Xue Leng, Wei Wang, Han Cen, Mo Zhou, Chen-Chen Feng, Yan Zhu, Xiao-Ke Yang, Mei Yang, Yu Zhai, Bao-Zhu Li, Xiao-Song Wang, R

Fuente: http://plos.srce.hr/



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