Genetic risk score for insulin resistance based on gene variants associated to amino acid metabolism in young adults

PLoS One. 2024 Feb 29;19(2):e0299543. doi: 10.1371/journal.pone.0299543. eCollection 2024.

Abstract

Circulating concentration of arginine, alanine, aspartate, isoleucine, leucine, phenylalanine, proline, tyrosine, taurine and valine are increased in subjects with insulin resistance, which could in part be attributed to the presence of single nucleotide polymorphisms (SNPs) within genes associated with amino acid metabolism. Thus, the aim of this work was to develop a Genetic Risk Score (GRS) for insulin resistance in young adults based on SNPs present in genes related to amino acid metabolism. We performed a cross-sectional study that included 452 subjects over 18 years of age. Anthropometric, clinical, and biochemical parameters were assessed including measurement of serum amino acids by high performance liquid chromatography. Eighteen SNPs were genotyped by allelic discrimination. Of these, ten were found to be in Hardy-Weinberg equilibrium, and only four were used to construct the GRS through multiple linear regression modeling. The GRS was calculated using the number of risk alleles of the SNPs in HGD, PRODH, DLD and SLC7A9 genes. Subjects with high GRS (≥ 0.836) had higher levels of glucose, insulin, homeostatic model assessment- insulin resistance (HOMA-IR), total cholesterol and triglycerides, and lower levels of arginine than subjects with low GRS (p < 0.05). The application of a GRS based on variants within genes associated to amino acid metabolism may be useful for the early identification of subjects at increased risk of insulin resistance.

MeSH terms

  • Adolescent
  • Adult
  • Alanine
  • Arginine
  • Cross-Sectional Studies
  • Genetic Risk Score
  • Humans
  • Insulin Resistance* / genetics
  • Young Adult

Substances

  • Alanine
  • Arginine

Grants and funding

This work was supported by CONACYT-202721 and CONACYT-CF2019-2096049 to LGN, by CONACYT-PN-2016-01-3324 to MGC, and by consultancy and industrial services 17 and 34 to JMVM from Facultad de Ciencias Químicas from the Universidad Autónoma de San Luis Potosí. There was no additional external funding received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.