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

Abstract

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.

Discovering Genetic Signatures Associated with Alzheimer’s Disease in Tiled Whole Genome Sequence Data: Results from the Artificial Intelligence for Alzheimer’s Disease (AI4AD) Consortium

“…As expected, the tile position -and therefore the tile variant containing (rs429358) -has the lowest p-value. Our results identify tile variants located in genes that are consistent with those found in other GWAS studies of AD or AD-related traits (Saunders et al 1993;Yan et al 2021;Coltell et al 2021;Davies et al 2018;Richardson et al 2022;van der Meer et al 2020;Shadrin et al 2021;Wang et al 2020;Homann et al 2022a), indicating that tiling and our model is likely effective and reliable . We filter the tile positions by a threshold of p-values < 1e-8.…”

The Polymorphism rs17300539 in the Adiponectin Promoter Gene Is Related to Metabolic Syndrome, Insulin Resistance, and Adiponectin Levels in Caucasian Patients with Obesity

“…This sample of the obese population increases by more than 10 points in BMI compared to our studied sample. The contradictory results in the above-mentioned investigations from the literature may be due to the type of population analysed: different ethnicities, the presence or absence of diabetes mellitus in the patients, different degrees of obesity, and different types of basal diets and amount of physical exercise [36].…”

The role of adiponectin in the association between abdominal obesity and type 2 diabetes: a mediation analysis among 232,438 Chinese participants

“…Coltell et al. suggested that the level of plasma adiponectin was not only strongly related to HDL-C and triglycerides but also inversely associated with fasting glucose and T2DM ( 22 ). Our results also indicated that adiponectin was inversely related to FPG, and patients with T2DM also presented with a lower level of circulating adiponectin (data were not shown).…”