The rs11187533 C>T Variant of the FFAR4 Gene Is Associated with Lower Levels of Fasting Glucose and Decreases in Markers of Liver Injury in Children with Obesity

Ann Nutr Metab. 2020;76(2):122-128. doi: 10.1159/000506618. Epub 2020 Apr 15.

Abstract

Introduction: Genetic factors can modulate the development of associated comorbidities in obesity. It has been shown that loss-of-function variants of the free fatty acid receptor 4 (FFAR4) gene negatively affect obesity comorbidities such as insulin resistance and fatty liver disease.

Objective: To test the relationships of metabolic factors in children with obesity with variants of the FFAR4 gene.

Methods: We performed an association study of 3 single nucleotide polymorphisms (SNPs) of FFAR4 (rs10882273 T>C, rs12243124 T>C, and rs11187533 C>T) covering the last intron and last exon of FFAR4 in a cohort of 203 children with obesity. Cardiometabolic factors were determined, including parameters related to insulin resistance, liver injury, and high-sensitivity C-reactive protein as an inflammatory marker.

Results: Significant genotype - phenotype interactions occurred between the rs11187533 SNP and glucose levels (p = 0.011). Moreover, we identified 2 marginally significant associations between this SNP and the hepatic enzymes alanine aminotransferase (p = 0.022) and gamma-glutamyltransferase (p = 0.015). The homozygous minor allele genotype (TT) was associated with a decrease in glucose levels.

Conclusion: The homozygous minor allele genotype of the rs11187533 SNP might be protective against metabolic consequences accompanying obesity and could allow the identification of metabolically healthy obese individuals at early ages.

Keywords: Gene; Obesity; Pediatrics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Alanine Transaminase / blood
  • Biomarkers / blood
  • Blood Glucose / analysis*
  • Body Mass Index
  • Child
  • Child, Preschool
  • Fasting
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Insulin Resistance / genetics
  • Liver / physiopathology
  • Liver Diseases / enzymology
  • Liver Diseases / genetics*
  • Male
  • Pediatric Obesity / complications
  • Pediatric Obesity / genetics*
  • Pediatric Obesity / physiopathology
  • Polymorphism, Single Nucleotide / genetics*
  • Receptors, G-Protein-Coupled / genetics*
  • gamma-Glutamyltransferase / blood

Substances

  • Biomarkers
  • Blood Glucose
  • FFAR4 protein, human
  • Receptors, G-Protein-Coupled
  • gamma-Glutamyltransferase
  • Alanine Transaminase