(P10-011-23) Serum Levels of Branched-Chain Amino Acids in Two Mediterranean Populations: Lifestyle, Genetics and Epigenetic Factors

Objectives: Branched-chain amino acids (BCAAs) are of great interest in precision nutrition due to their adverse effects associated with increased insulin resistance and other cardiovascular disorders. In the Mediterranean population, however, there have been few studies of BCCAs. Our objective was to analyze associations of BCAAs with cardiometabolic risk factors in two Mediterranean populations and to assess the influence of lifestyle, genetic, and epigenetic factors.

Methods: We conducted a cross-sectional study on 651 individuals from the Spanish Mediterranean population. 426 subjects were of high cardiovascular risk, while 225 were drawn from the general population of the same region .Using nuclear magnetic resonance, BCAA (leucine, isoleucine, and valine) levels were measured on an international platform for metabolomics. Anthropometric, clinical and lifestyle data were collected, and multiple regression models and quantile-g-computation were used to examine the associations. Illumina arrays were used for genotyping and conduct exploratory genome-wide association studies (GWAS). The Illumina EPIC 850K methylation array was for DNA-methylation and conduct epigenome-wide association studies (EWAS).

Results: BCAA concentrations were greater the high cardiovascular risk subjects compared to the general population (p < 0.05). In the high risk population, levels for leucine, isoleucine, and valine were 0.092+/-0.019, 0.070 +/-0.017, and 0.199+/-0.037 mmol/l, respectively. These BCAAs were strongly associated with fasting glucose in the high-risk population (p < 0.01) and with obesity in the general population (p < 0.01). Mediterranean diet adherence was inversely associated with BCAA levels (p < 0.05), being meat intake the food more positively associated with BCAA (p < 0.05). We identified some SNPs in the GWASs associated with BCAA, but these SNPs were not the expected from other GWAS (SNPs in the PPM1K gene, or in the GCKR gene, among others). Likewise we identified several differentially methylated CpG sites associated with BCAAs in this population.

Conclusions: The associations between genetic, epigenetic and dietary factors and BCAAs levels are different depending on the population, so it cannot be generalized in precision nutrition.

Funding Sources: Generalitat Valenciana PROMETEO/2021/021; ISCIII-CIBER 06/03; AEI PID2019-108858RB-I00