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

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.