Background: Cardiometabolic risk results from interactions between genetic and dietary factors. Variation in the adrenergic β-2 receptor gene (ADRB2 rs1042713) may influence responses to insulinogenic dietary patterns.

Objectives: We aimed to assess whether the associations between dietary insulin indices (DIIs) and cardiometabolic risk factors differ by ADRB2 rs1042713 genotype.

Methods: In this cross-sectional study involving 369 adults, the energy-adjusted DII and dietary insulin loads (DILs) were derived from a validated food frequency questionnaire. The rs1042713 polymorphism was genotyped using the polymerase chain reaction-restriction fragment length method. Gene-diet interactions were assessed using multivariable general linear models.

Results: Significant interactions were observed between both DII and DIL and the rs1042713 genotype on systolic blood pressure (SBP) (P-interaction < 0.05). In tertile analyses, among A-allele carriers, SBP was 7.8-7.9 mm Hg in the highest versus lowest tertiles of both DIL and DII (95% CIs = 2.5, 13.2 mm Hg). In contrast, among GG homozygotes, SBP was slightly lower in the highest DII tertile compared with the lowest tertile. A modest interaction between DIL and genotype was observed for HDL cholesterol (P = 0.035), which was attenuated after adjustment (P = 0.056). Interactions with diastolic blood pressure were inconsistent.

Conclusions: The associations between insulinogenic dietary patterns and SBP vary by ADRB2 rs1042713 genotype, with greater sensitivity among A-allele carriers and a more attenuated response among GG homozygotes. SBP emerged as the most consistent outcome, highlighting the need for confirmation in prospective studies.