ABSTRACT

Background and objective:
Hypertension is influenced by both genetic and dietary factors. Understanding gene-diet interactions across populations is key to precision prevention.

Objectives:
To identify genetic variants associated with hypertension in KoGES and UK Biobank (UKBB), and evaluate their interactions with nutrient intake.

Subjects/methods:
Genome-wide association analyses were conducted for hypertension (HTN: SBP ≥ 140 mmHg, DBP ≥ 90 mmHg or taking hypotensive medication) in KoGES (Non-HTN, n = 39,387; HTN, n = 13,727) and replicated in UKBB (Non-HTN, n = 334,785; HTN, n = 132,140). Genetic risk scores (GRS) were constructed from seven common SNPs. Genetic variant or GRS-diet interactions were analyzed via logistic regression.

Results:
Common SNPs in genes such as FGF5, CYP17A1, CNNM2, AS3MT, ATP2B1, BORCS7-ASMT, NT5C2, and RGL3 were significantly linked to hypertension in both cohorts (P < 5 × 10⁻⁸). In KoGES, the associated genes were enriched in lipid metabolism pathways. In UKBB, vascular signaling pathways, including AKT1, MAPK, and TGF-β signaling, were predominant based on the selected genetic variants. Despite common variants, distinct biological mechanisms were implicated in Koreans and Caucasians. The GRS of the 6-SNP model, including FGF5, CYP17A1, CNNM2, ATP2B1, BORCS7-ASMT, and RGL3, was associated with hypertension risk. However, this effect was attenuated with high tea and coffee intake only in the low-GRS individuals in both cohorts (P < 0.05). The RGL3 rs167479 variant showed significant interactions with vitamins C, D, B12, and flavonoids in KoGES (P = 0.02-0.002).

Conclusions:
Common genetic variants contribute to hypertension across populations but act through divergent molecular pathways. Targeted nutrient intake appears to mitigate genetic risk, underscoring the promise of gene-informed dietary strategies for hypertension prevention.

‍