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.

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

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.

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.

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.