Circulating Adiponectin and Its Association with Metabolic Traits and Type 2 Diabetes: Gene-Diet Interactions Focusing on Selected Gene Variants and at the Genome-Wide Level in High-Cardiovascular Risk Mediterranean Subjects

Nutrients. 2021 Feb 7;13(2):541. doi: 10.3390/nu13020541.


Adiponectin is gaining renewed interest since, in addition to its possible protective role against insulin resistance and arteriosclerosis, recent studies suggest other additional favorable effects. However, the influence of gene-diet interactions on plasma adiponectin levels is still little understood. We analyzed the association between plasma adiponectin levels and various metabolic traits in a high-cardiovascular risk Mediterranean population, as well as the genetic effect of four candidate single-nucleotide polymorphisms (SNPs) in the adiponectin gene (ADIPOQ) and their interactions with the Mediterranean dietary pattern. Additionally, we explored, at the genome-wide level, the SNPs most associated with plasma adiponectin levels, as well as gene-diet interactions with the Mediterranean diet. In the 954 participants studied (aged 55-80 years), plasma adiponectin levels were strongly associated with plasma HDL-C concentrations (p = 6.6 × 10-36) and inversely related to triglycerides (p = 4.7 × 10-18), fasting glucose (p = 3.5 × 10-16) and type 2 diabetes (p = 1.4 × 10-7). Of the four pre-selected ADIPOQ candidate SNPs, the one most associated with plasma adiponectin was the -11391G > A (rs17300539) promoter SNP (p = 7.2 × 10-5, in the multivariable adjusted model). No significant interactions with the Mediterranean diet pattern were observed for these SNPs. Additionally, in the exploratory genome-wide association study (GWAS), we found new SNPs associated with adiponectin concentrations at the suggestive genome-wide level (p < 1 × 10-5) for the whole population, including the lead SNP rs9738548 (intergenic) and rs11647294 in the VAT1L (Vesicle Amine Transport 1 Like) gene. We also found other promising SNPs on exploring different strata such as men, women, diabetics and non-diabetics (p = 3.5 × 10-8 for rs2850066). Similarly, we explored gene-Mediterranean diet interactions at the GWAS level and identified several SNPs with gene-diet interactions at p < 1 × 10-5. A remarkable gene-diet interaction was revealed for the rs2917570 SNP in the OPCML (Opioid Binding Protein/Cell Adhesion Molecule Like) gene, previously reported to be associated with adiponectin levels in some populations. Our results suggest that, in this high-cardiovascular risk Mediterranean population, and even though adiponectin is favorably associated with metabolic traits and lower type 2 diabetes, the gene variants more associated with adiponectin may be population-specific, and some suggestive gene-Mediterranean diet interactions were detected.

Keywords: Mediterranean diet; adiponectin; body mass index; genetics; gene–diet interactions; genome-wide association study; plasma lipids; polymorphisms; type 2 diabetes.

MeSH terms

  • Adiponectin / blood*
  • Adiponectin / genetics*
  • Aged
  • Aged, 80 and over
  • Cardiovascular Diseases / etiology*
  • Cardiovascular Diseases / genetics*
  • Diabetes Mellitus, Type 2 / genetics*
  • Diet, Mediterranean*
  • Female
  • Genome-Wide Association Study*
  • Humans
  • Male
  • Metabolic Syndrome / genetics*
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Risk
  • Vesicular Transport Proteins / genetics


  • Adiponectin
  • VAT1 protein, human
  • Vesicular Transport Proteins