Articular cartilage is an avascular tissue with a structure that allows it to support and cushion the overload of the surfaces in contact. It maintains its metabolic functions due to the contribution of different signaling pathways. However, several factors play a role in its deterioration, allowing to the development of osteoarthritis (OA), and one of the major factors is genetic. Our goal was to identify gene-gene interactions (epistasis) between five signaling pathways involved in the articular cartilage metabolism as possible indicators of OA risk. We applied the Multifactor-Dimensionality Reduction (MDR) method to identify and characterize the epistasis between 115 SNPs located in 73 genes related to HIF-1α, Wnt/β-catenin, cartilage extracellular matrix metabolism, oxidative stress, and uric acid transporters. Ninety three patients diagnosed with primary knee OA and 150 healthy controls were included in the study. Genotyping was performed with the OpenArray system, the statistical analysis was carried out with the STATA software v14, and epistasis was analyzed with the MDR software v3.0.2. The MDR analysis revealed that the best interaction model was between polymorphisms rs17786744 of the STC1 gene and rs2615977 of the COL11A1 gene, with an entropy value of 4.44%, CVC 8/10, OR 5.60, 95% CI 3.27-9.59, p < 0.0001. Under this interaction model, we identified high and low risk genotypes involved in OA development. Our results suggest complex interactions between STC1 and COL11A1 genes that might have an impact on genetic susceptibility to develop OA. Further studies are required to confirm it.

中文翻译：

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多因素维度的减少揭示了STC1和COL11A1基因之间强大的基因-基因相互作用，可能是膝骨关节炎的危险因素。

关节软骨是一种无血管组织，其结构使其可以支撑和缓冲接触表面的过载。由于不同信号途径的贡献，其维持其代谢功能。然而，多种因素在其恶化中起作用，从而导致骨关节炎（OA）的发展，并且主要因素之一是遗传。我们的目标是确定参与关节软骨代谢的五个信号通路之间的基因-基因相互作用（表皮）作为OA风险的可能指标。我们应用多维度降维（MDR）方法来鉴定和表征位于与HIF-1α，Wnt /β-catenin，软骨细胞外基质代谢，氧化应激和尿酸转运蛋白相关的73个基因中的115个SNP之间的上位性。这项研究包括了93名被诊断患有原发性膝关节炎的患者和150名健康对照。使用OpenArray系统进行基因分型，使用STATA软件v14进行统计分析，并使用MDR软件v3.0.2分析上位性。MDR分析表明，最佳相互作用模型是STC1基因的多态性rs17786744与COL11A1基因的rs2615977之间的熵值，熵值为4.44％，CVC 8/10或OR 5.60、95％CI 3.27-9.59，p <0.0001 。在这种相互作用模型下，我们确定了OA发展中涉及的高风险和低风险基因型。我们的研究结果表明，STC1和COL11A1基因之间的复杂相互作用可能会对发展OA的遗传易感性产生影响。需要进一步研究以确认这一点。