黄酮类化合物在人类中发挥血管保护作用,但他们行动中的个体间差异也有报道。这项研究旨在确定与类黄酮对血管健康影响相关的基因,其多态性可以解释个体间对其摄入量的反应。应用预定的文献检索标准,我们确定了5项人类干预研究,这些研究报告了黄酮类化合物对血管功能的积极作用以及使用微阵列方法分析的全球基因组变化.从全基因组关联研究(GWAS)中鉴定了与血管功能障碍有关的基因。通过从符合条件的人类干预研究中提取数据,我们获得了5807个差异表达基因(DEGs)。在研究中,确定的上游监管机构(URs)的数量各不相同,从227到1407。GWAS目录的搜索揭示了493个与血管功能障碍相关的基因。使用GWAS基因对转录组数据进行综合分析,确定了106个候选DEG和42个候选URs,而随后的功能分析和文献搜索确定了20个最优先的候选基因:ALDH2,APOE,CAPZA1,CYP11B2,GNA13,IL6,IRF5,LDLR,LPL,LSP1,MKNK1,MMP3,MTHFR,MYO6,NCR3,PPARG,SARM1、TCF20、TCF7L2和TNF。总之,这项综合分析确定了重要的基因,以设计未来的营养遗传学研究,以开发多酚的精确营养。
Flavonoids exert vasculoprotective effects in humans, but interindividual variability in their action has also been reported. This study aims to identify genes that are associated with vascular health effects of flavonoids and whose polymorphisms could explain interindividual variability in response to their intake. Applying the predetermined literature search criteria, we identified five human intervention studies reporting positive effects of flavonoids on vascular function together with global genomic changes analyzed using microarray methods. Genes involved in vascular dysfunction were identified from genome-wide association studies (GWAS). By extracting data from the eligible human intervention studies, we obtained 5807 differentially expressed genes (DEGs). The number of identified upstream regulators (URs) varied across the studies, from 227 to 1407. The search of the GWAS Catalog revealed 493 genes associated with vascular dysfunction. An integrative analysis of transcriptomic data with GWAS genes identified 106 candidate DEGs and 42 candidate URs, while subsequent functional analyses and a search of the literature identified 20 top priority candidate genes: ALDH2, APOE, CAPZA1, CYP11B2, GNA13, IL6, IRF5, LDLR, LPL, LSP1, MKNK1, MMP3, MTHFR, MYO6, NCR3, PPARG, SARM1, TCF20, TCF7L2, and TNF. In conclusion, this integrated analysis identifies important genes to design future nutrigenetic studies for development of precision nutrition for polyphenols.