Integrated analysis of genomic and genome-wide association studies identified candidate genes for nutrigenetic studies in flavonoids and vascular health: path to precision nutrition for (poly)phenols

Background:
Flavonoids exert vasculoprotective effects in humans, but considerable interindividual variability in their response has been reported. Genetic differences may partly explain this variability, particularly polymorphisms in genes involved in vascular function and metabolic regulation. Understanding the molecular mechanisms underlying the vascular effects of flavonoids may support the development of precision nutrition approaches targeting cardiovascular health.
Aims:
This study aimed to identify genes associated with vascular health effects of flavonoids and to determine candidate genes whose polymorphisms could explain interindividual variability in response to flavonoid intake.
Results:
Using predefined literature search criteria, five human intervention studies reporting beneficial effects of flavonoids on vascular function and analyzing global genomic changes using microarray methods were identified. From these studies, 5807 differentially expressed genes (DEGs) were extracted. The number of identified upstream regulators (URs) ranged from 227 to 1407 across the studies. Additionally, genes involved in vascular dysfunction were identified from genome-wide association studies, yielding 493 genes from the GWAS Catalog. Integrative analysis combining transcriptomic data from intervention studies with GWAS-derived genes identified 106 candidate DEGs and 42 candidate URs. Subsequent functional analyses and literature review highlighted 20 top priority candidate genes, including ALDH2, APOE, CYP11B2, IL6, LDLR, LPL, MMP3, MTHFR, PPARG, TCF7L2, and TNF.
Main Objective:
To integrate transcriptomic data from flavonoid intervention studies with genetic evidence from genome-wide association studies in order to identify key candidate genes involved in vascular responses to flavonoid intake.
Conclusion:
This integrative analysis identifies candidate genes potentially involved in the vascular effects of flavonoids and provides a basis for future nutrigenetic studies aimed at understanding interindividual variability and developing precision nutrition strategies for cardiovascular disease prevention.