Lifestyle genomics and the metabolic syndrome: A review of genetic variants that influence response to diet and exercise interventions

Crit Rev Food Sci Nutr. 2019;59(13):2028-2039. doi: 10.1080/10408398.2018.1437022. Epub 2018 Mar 1.


Metabolic syndrome (MetS) comprises a cluster of risk factors that includes central obesity, dyslipidemia, impaired glucose homeostasis and hypertension. Individuals with MetS have elevated risk of type 2 diabetes and cardiovascular disease; thus placing significant burdens on social and healthcare systems. Lifestyle interventions (comprised of diet, exercise or a combination of both) are routinely recommended as the first line of treatment for MetS. Only a proportion of people respond, and it has been assumed that psychological and social aspects primarily account for these differences. However, the etiology of MetS is multifactorial and stems, in part, on a person's genetic make-up. Numerous single nucleotide polymorphisms (SNPs) are associated with the various components of MetS, and several of these SNPs have been shown to modify a person's response to lifestyle interventions. Consequently, genetic variants can influence the extent to which a person responds to changes in diet and/or exercise. The goal of this review is to highlight SNPs reported to influence the magnitude of change in body weight, dyslipidemia, glucose homeostasis and blood pressure during lifestyle interventions aimed at improving MetS components. Knowledge regarding these genetic variants and their ability to modulate a person's response will provide additional context for improving the effectiveness of personalized lifestyle interventions that aim to reduce the risks associated with MetS.

Keywords: Diet-Gene Interaction; Exercise-Gene Interaction; Lifestyle Intervention; Metabolic Syndrome; Single Nucleotide Polymorphism.

Publication types

  • Review

MeSH terms

  • Apolipoprotein A-V / genetics
  • Apolipoprotein A-V / metabolism
  • Apolipoproteins E / genetics
  • Apolipoproteins E / metabolism
  • Blood Pressure
  • Body Weight
  • Diet*
  • Dyslipidemias / genetics
  • Dyslipidemias / therapy
  • Exercise*
  • Genomics*
  • Health Behavior
  • Homeostasis
  • Humans
  • Insulin Receptor Substrate Proteins / genetics
  • Insulin Receptor Substrate Proteins / metabolism
  • Life Style*
  • Metabolic Syndrome / genetics*
  • Metabolic Syndrome / therapy
  • Obesity / genetics
  • Obesity / therapy
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Polymorphism, Single Nucleotide
  • Randomized Controlled Trials as Topic
  • Receptor, Melanocortin, Type 4 / genetics
  • Receptor, Melanocortin, Type 4 / metabolism
  • Receptors, Adrenergic, beta-3 / genetics
  • Receptors, Adrenergic, beta-3 / metabolism
  • Transcription Factor 7-Like 2 Protein / genetics
  • Transcription Factor 7-Like 2 Protein / metabolism


  • ADRB3 protein, human
  • Apolipoprotein A-V
  • Apolipoproteins E
  • IRS1 protein, human
  • Insulin Receptor Substrate Proteins
  • MC4R protein, human
  • PPAR gamma
  • Receptor, Melanocortin, Type 4
  • Receptors, Adrenergic, beta-3
  • TCF7L2 protein, human
  • Transcription Factor 7-Like 2 Protein