Background Variability in circulating carotenoids may be attributable to several factors including, among others, genetic variants and lipid profile. However, relatively few studies have considered the impact of gene expression in the inter-individual variability in circulating carotenoids. Most studies considered expression of genes individually and ignored their high degree of interconnection. Weighted gene co-expression network analysis (WGCNA) is a systems biology method used for finding gene clusters with highly correlated expression levels and for relating them to phenotypic traits. The objective of the present observational study is to examine the relationship between plasma total carotenoid concentrations and lipid profile using WGCNA. Results Whole blood expression levels of 533 probes were associated with plasma total carotenoids. Among the four WGCNA distinct modules identified, turquoise, blue, and brown modules correlated with plasma high-density lipoprotein cholesterol (HDL-C) and total cholesterol. Probes showing a strong association with HDL-C and total cholesterol were also the most important elements of the brown and blue modules. A total of four and 29 hub genes associated with total carotenoids were potentially related to HDL-C and total cholesterol, respectively. Conclusions Expression levels of 533 probes were associated with plasma total carotenoid concentrations. Using WGCNA, four modules and several hub genes related to lipid and carotenoid metabolism were identified. This integrative analysis provides evidence for the potential role of gene co-expression in the relationship between carotenoids and lipid concentrations. Further studies and validation of the hub genes are needed.

中文翻译：

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加权基因共表达网络分析解释血浆总类胡萝卜素与脂质谱之间的关系。

背景 循环类胡萝卜素的变异性可归因于几个因素，其中包括遗传变异和脂质谱。然而，相对较少的研究考虑了基因表达对循环类胡萝卜素个体间变异性的影响。大多数研究单独考虑基因的表达，而忽略了它们的高度相互联系。加权基因共表达网络分析 (WGCNA) 是一种系统生物学方法，用于寻找具有高度相关表达水平的基因簇并将它们与表型性状相关联。本观察性研究的目的是使用 WGCNA 检查血浆总类胡萝卜素浓度与脂质分布之间的关系。结果533个探针的全血表达水平与血浆总类胡萝卜素相关。在确定的四个 WGCNA 不同模块中，绿松石、蓝色和棕色模块与血浆高密度脂蛋白胆固醇 (HDL-C) 和总胆固醇相关。与 HDL-C 和总胆固醇密切相关的探针也是棕色和蓝色模块中最重要的元素。与总类胡萝卜素相关的中枢基因共有 4 个和 29 个，分别可能与 HDL-C 和总胆固醇有关。结论 533个探针的表达水平与血浆总类胡萝卜素浓度相关。使用 WGCNA，确定了与脂质和类胡萝卜素代谢相关的四个模块和几个中心基因。这种综合分析为基因共表达在类胡萝卜素和脂质浓度之间的关系中的潜在作用提供了证据。