Variants in APOA5 and ADIPOQ Moderate Improvements in Metabolic Syndrome during a One-Year Lifestyle Intervention

Lifestyle Genom. 2018;11(2):80-89. doi: 10.1159/000494331. Epub 2018 Nov 23.


Background: Metabolic syndrome (MetS) comprises a cluster of risk factors including central obesity, hypertension, dyslipidemia, and impaired glucose homeostasis. Lifestyle interventions that promote improvements in diet quality and physical activity represent a first line of therapy for MetS. However, varying responses to lifestyle interventions are well documented and may be partially explained by underlying genetic differences. The aim of this study was to investigate if variants in genes previously associated with MetS influence the magnitude of change in MetS risk during a 1-year lifestyle intervention.

Methods: The present study used data collected from the Canadian Health Advanced by Nutrition and Graded Exercise study cohort (n = 159 men and women) to investigate the effect of 17 candidate single nucleotide polymorphisms (SNPs) on response to a 1-year lifestyle intervention. Associations between SNPs and the continuous MetS (cMetS) score, as well as individual MetS components, were examined.

Results: Reductions in cMetS score at both 3 months and 1 year were significantly associated with 2 variants: rs662799 (A/G) in apolipoprotein A5 (APOA5) and rs1501299 (G/T) in adiponectin (ADIPOQ). Individuals carrying a minor T allele in rs1501299 experienced a greater reduction in cMetS score at both 3 months and 1 year, whereas major allele AA homozygotes in rs662799 experienced greater reductions in cMetS score during the intervention. No associations were identified between the aforementioned SNPs and individual components of MetS. Both un-weighted and weighted genetic risk scores (GRS) using these 2 SNPs revealed that individuals carrying none of the risk alleles experienced significantly greater reductions in cMetS score after 1 year.

Conclusions: The findings from the current study suggest that individuals with certain genotypes may benefit more from a lifestyle intervention for MetS and that specific variants, either independently or as part of a GRS, could be used as a nutrigenomic tool to tailor the intervention to reduce the risk of MetS.

Keywords: Continuous MetS score; Gene association; Lifestyle intervention; Metabolic syndrome; Nutrigenomics; Single nucleotide polymorphism.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / genetics*
  • Adolescent
  • Adult
  • Aged
  • Apolipoprotein A-V / genetics*
  • Behavior Therapy / methods*
  • Canada
  • Combined Modality Therapy
  • Diet, Mediterranean
  • Exercise Therapy
  • Feasibility Studies
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Life Style*
  • Longitudinal Studies
  • Male
  • Metabolic Syndrome / genetics*
  • Metabolic Syndrome / prevention & control*
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Risk Reduction Behavior
  • Time Factors
  • Young Adult


  • ADIPOQ protein, human
  • APOA5 protein, human
  • Adiponectin
  • Apolipoprotein A-V