Genetic variability determines cardiometabolic response to orange juice and hesperidin intake

Objectives: Several clinical studies have suggested that intake of orange juice and/or hesperidin has a positive effect on health outcomes. However, large interindividual variability in response has been described, which could be attributed to different factors, including genetic polymorphisms described in one study. The aim of our study was to evaluate the effect of orange juice and hesperidin intake on cardiometabolic parameters and assess the association between genetic polymorphisms of key genes (identified as target genes of orange juice (OJ) and hesperidin (HESP) based on the integration of gene expression analyses and GWAS) and the response of these parameters (blood pressure, arterial stiffness, blood lipids, and markers of vascular function).
Methods: A randomized, 3-arm, crossover study, was conducted in 37 men, 40-65 y old, BMI ≤30 kg/m2, waist circumference >94 cm, and otherwise healthy, who daily consumed A) orange juice (providing 200 mg hesperidin/day); B) sugary drink (placebo); C) sugary drink + 200 mg HESP, for 6 weeks. Cardiometabolic parameters were measured and genetic polymorphisms of 21 genes were assessed. SNP association analyses were performed using SNPStats in volunteers presenting higher than median polyphenol excretion level.
Results: No significant changes in cardiometabolic parameters were observed following OJ and HESP intake. However, significant associations were observed between target SNPs and individual responses. For example, a significant association between SNPs and ICAM1 level, total cholesterol, and systolic blood pressure after HESP intake was observed. rs10224002 in PRKAG2 gene was associated with ICAM1, SNP identified to impact vascular function. Similarly, significant associations were observed between SNPs and selectin, pulse pressure, and diastolic blood pressure after OJ intake. Subgroup analysis showed a significant effect on these parameters for both OJ and HESP depending on the genotype of these SNPs.
Conclusions: The positive health effects of OJ and HESP can be affected by genetic polymorphisms of target genes, providing novel data for future precision nutrition.