Role of beta-2 adrenergic receptor polymorphism (rs1042714) on body weight and glucose metabolism response to a meal-replacement hypocaloric diet

Abstract

Objectives: The beta-2 adrenergic receptor (ADRB2) is involved in energy balance regulation. The objective of our study was to evaluate the role of the rs1042714 genetic variant of ADRB2 gene on weight loss, body composition, and metabolic changes secondary to partial meal replacement (pMR) hypocaloric diet in women with obesity.

Methods: We conducted an interventional study in 95 premenopausal women with body mass index ≥ 35 kg/m². The subjects received two intakes per day of a normocaloric hyperproteic formula during 12 wk of a pMR diet. Body weight, body mass index, fat mass, waist circumference, lipid profile, fasting insulin levels, and homeostasis model assessment for insulin resistance were determined. All patients were genotyped rs1042714 and evaluated in a dominant model (CC versus CG + GG).

Results: Genotype frequencies were 31 (37.3%), 38 (45.8%), and 14 (16.9%) for the CC, CG, and GG genotypes, respectively. We found significant interaction effects between ADRB2 variant and pMR-induced changes (CC versus CG + GG) on body weight (-7.1 ± 0.3 versus -13.5 ± 0.5 kg; P = 0.03), body mass index (-0.9 ± 0.1 versus -1.2 ± 0.2 kg/m²; P = 0.03), fat mass (-4.9 ± 0.5 versus -10.2 ±1.2 kg; P = 0.01), waist circumference (-5.1 ± 0.2 versus -10.1 ± 1.9 cm; P = 0.03), glucose (-5.1 ± 1.3 versus -12.5 ± 2.5 mg/dL; P = 0.03), total cholesterol (-18.1 ± 9.3 versus -33.5 ± 4.5 mg/dL; P = 0.03), low-density lipoprotein cholesterol (-9.1 ± 5.3 versus -24.5 ± 4.1 mg/dL; P = 0.04), triacylglycerol levels (-6.1 ± 5.3 versus -31.5 ± 9.5 mg/dL; P = 0.04), fasting insulin levels (-1.8 ± 0.3 versus -6.3 ± 0.5 IU/L; P = 0.03), and homeostasis model assessment for insulin resistance (-0.6 ± 0.3 versus -1.9 ± 0.5 U; P = 0.03). The odds ratio to improve alteration in glucose metabolism adjusted by age and weight loss throughout the study was 0.26 (95% CI, 0.07-0.95; P = 0.02) in G allele carriers.

Conclusions: The G allele of rs1042714 predicts the magnitude of weight loss resulting from a pMR diet. These adiposity improvements produce a better improvement of insulin resistance and percentage of impaired glucose metabolism in G allele carriers.

Keywords: ADBR2 gene; Beta-2 adrenergic receptor; Body weight; Partial meal replacement; rs1042714.