The Combined Effect of Polygenic Risk from FTO and ADRB2 Gene Variants, Odds of Obesity, and Post-Hipcref Diet Differences

Lifestyle Genom. 2020;13(2):84-98. doi: 10.1159/000505662. Epub 2020 Feb 26.

Abstract

Background: Computing polygenic risk scores (PRS) to predict the degree of risk for obesity may contribute to weight management programs strategically.

Objectives: To investigate the combined effect of FTO rs9930501, rs9930506, and rs9932754 and ADRB2 rs1042713 and rs1042714 using PRS on (1) the odds of obesity and (2) post-intervention differences in dietary, anthropometric, and cardiometabolic parameters in response to high-protein calorie-restricted, high-vitamin E, high-fiber (Hipcref) diet intervention in Malaysian adults.

Methods: Both a cross-sectional study (n = 178) and a randomized controlled trial (RCT) (n = 128) were conducted to test the aforementioned objectives. PRS was computed as the weighted sum of the risk alleles possessed by each individual participant. Participants were stratified into first (PRS 0-0.64), second (PRS 0.65-3.59), and third (PRS 3.60-8.18) tertiles.

Results: The third tertile of PRS was associated with significantly higher odds of obesity: 2.29 (95% CI = 1.11-4.72, adjusted p = 0.025) compared to the first tertile. Indians (3.9 ± 0.3) had significantly higher PRS compared to Chinese (2.1 ± 0.4) (p = 0.010). In the RCT, a greater reduction in high-sensitivity C-reactive protein (hsCRP) levels was found in second and third tertiles after Hipcref diet intervention compared to the control diet (p interaction = 0.048).

Conclusion: Higher PRS was significantly associated with increased odds of obesity. Individuals with higher PRS had a significantly greater reduction in hsCRP levels after Hipcref diet compared to the control diet.

Keywords: Hipcref diet intervention; Malaysian adults; Obesity; Polygenic risk scores; Post-intervention differences.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alleles
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO / genetics*
  • Anthropometry
  • Body Weight
  • C-Reactive Protein / metabolism
  • Cross-Sectional Studies
  • Diet*
  • Diet, Reducing
  • Dietary Fiber
  • Energy Intake
  • Ethnicity
  • Female
  • Gene-Environment Interaction
  • Genetic Predisposition to Disease*
  • Genetic Variation*
  • Genotype
  • Humans
  • Malaysia / epidemiology
  • Male
  • Middle Aged
  • Obesity / genetics*
  • Odds Ratio
  • Overweight
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Receptors, Adrenergic, beta-2 / genetics*
  • Risk
  • Vitamin E / metabolism
  • Young Adult

Substances

  • ADRB2 protein, human
  • Dietary Fiber
  • Receptors, Adrenergic, beta-2
  • Vitamin E
  • C-Reactive Protein
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • FTO protein, human