Gene-gene interactions of the Wnt/β-catenin signaling pathway in knee osteoarthritis
Gene-gene interactions of the Wnt/β-catenin signaling pathway in knee osteoarthritis
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DOI：
10.1007/s11033-018-4260-2
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发表时间：
2018-10-01
影响因子：
2.8
通讯作者：
Angelica Martinez-Nava, Gabriela
中科院分区：
文献类型：
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作者：
Fernandez-Torres, Javier;Zamudio-Cuevas, Yessica;Angelica Martinez-Nava, Gabriela
本研究旨在探讨Wnt/β-catenin信号通路基因多态性及其相互作用是否参与膝骨性关节炎(KOA)的发生发展。对131例膝关节骨性关节炎患者和190例来自墨西哥城和瓜达拉哈拉两个墨西哥人群的不同血统的健康人进行了分析。对涉及Wnt/β-catenin信号通路的13个基因(WISP1、Dkk1、SOST、FRZB、LRP1、LRP4、LRP5、LRP6、GSKB、ADAMTS5、GDF5、FMN2和COL11A1)的25个SNP进行了基因分型。对遗传频率、等位基因频率和基因-基因互作进行了分析。在调整了年龄、性别、体重指数和混合因素后，发现5个SNP与墨西哥城人群显著相关：LRP6rs12314259(G/G型OR0.22，P=0.029；G等位基因OR0.48，P=0.022)，SOST rs851054(C/T型OR0.42，P=0.027；T等位基因OR0.62，P=0.026)，FMN2rs986690(G/A型OR0.42，P=0.034；A等位基因OR0.50(P=0.015)、FRZBrs409238(A/G基因型，OR2.41，P=0.022)和COL11A1 rs2615977(A/C基因型OR2.39，P=0.024)，未发现与瓜达拉哈拉的关联。在基因-基因互作方面，WISP1-COL11A1、COL11A1-FRZB、FRZB-SOST和WISP1-FMN2的成对交互作用使我们能够直观地看到它们的基因型或等位基因在两个群体中的协同或拮抗效应。这些结果表明，Wnt/β-catenin信号通路中的基因-基因相互作用在KOA的发病机制中起一定作用。
This study was designed to investigate whether genetic polymorphisms of the Wnt/beta-catenin signaling pathway and its interactions are involved in the development of knee osteoarthritis (KOA). Patients with KOA (n = 131) and healthy individuals (n = 190) with different ancestry from two Mexican populations (Mexico City and Guadalajara City) were analyzed. Twenty-five SNPs from thirteen genes (WISP1, DKK1, SOST, FRZB, LRP1, LRP4, LRP5, LRP6, GSKB, ADAMTS5, GDF5, FMN2 and COL11A1) involved in the Wnt/beta-catenin signaling pathway were genotyped. Genetic and allelic frequencies and gene-gene interactions were performed for this study. After adjusting for age, sex, BMI and admixture, significant associations were found for five SNPs in Mexico City: LRP6 rs12314259 (G/G genotype OR 0.22, P = 0.029; and G allele OR 0.48, P = 0.022), SOST rs851054 (C/T genotype OR 0.42, P = 0.027; and T allele OR 0.62, P = 0.026), FMN2 rs986690 (G/A genotype OR 0.42, P = 0.034; and A allele OR 0.50, P = 0.015), FRZB rs409238 (A/G genotype, OR 2.41, P = 0.022), and COL11A1 rs2615977 (A/C genotype OR 2.39, P = 0.024); no associations for Guadalajara City were found. With respect to gene-gene interactions, the pairwise interactions of WISP1-COL11A1, COL11A1-FRZB, FRZB-SOST and WISP1-FMN2 make it possible to visualize the synergistic or antagonistic effect of their genotypes or alleles in both populations. These results suggest that gene-gene interactions in the Wnt/beta-catenin signaling pathway play a role in the etiology of KOA.