Novel Association Between a Nonsynonymous Variant (R270H) of the G‐Protein–Coupled Receptor 120 and Liver Injury in Children and Adolescents With Obesity
Copyright policy )Novel Association Between a Nonsynonymous Variant (R270H) of the G‐Protein–Coupled Receptor 120 and Liver Injury in Children and Adolescents With Obesity
ABSTRACTThe G‐protein–coupled receptor 120 (GPR120) is a receptor for polyunsaturated fatty acids with anti‐inflammatory activity. The R270H variant of GPR120 enhances inflammation in adipose and hepatic tissues. We investigated whether the R270H variant could play a role in determining liver injury in children and adolescents with obesity. Five hundred eighty‐one children with obesity were studied. No homozygotes and 20 heterozygotes for the 270H allele were found. Heterozygotes showed higher alanine transaminase (ALT) levels (P = 0.01) than wild‐type subjects, and also showed an odds ratio to have pathologic ALT of 3.2 (95% confidence interval [CI] 1.2–8.0, P < 0.05). Moreover, we genotyped the same patients for the patatin‐like phospholipase‐containing domain 3 (PNPLA3) I148M polymorphism, which is implicated in the development of liver steatosis. Stratifying the patients with the GPR120 270H variant on the basis of their PNPLA3 polymorphism, we demonstrated a significant interaction effect on ALT levels (P = 0.00001), suggesting a driving effect of the PNPLA3 148M allele on liver injury in children with obesity carrying this variant.
Male, Heterozygote, Pediatric Obesity, Adolescent, Genotype, Alanine transaminase; G-protein-coupled receptor 120; Nonalcoholic fatty liver disease; Patatin-like phospholipasecontaining domain 3; Pediatric obesity; Adipose Tissue; Adolescent; Alanine Transaminase; Alleles; Child; Child, Preschool; Fatty Acids, Unsaturated; Fatty Liver; Female; Heterozygote; Humans; Inflammation; Lipase; Liver; Male; Membrane Proteins; Odds Ratio; Pediatric Obesity; Receptors, G-Protein-Coupled; Genotype; Polymorphism, Genetic, Odds Ratio, Humans, Child, Alleles, Inflammation, Polymorphism, Genetic, Membrane Proteins, Alanine Transaminase, Lipase, Fatty Liver, Adipose Tissue, Liver, Child, Preschool, Fatty Acids, Unsaturated, Female
Male, Heterozygote, Pediatric Obesity, Adolescent, Genotype, Alanine transaminase; G-protein-coupled receptor 120; Nonalcoholic fatty liver disease; Patatin-like phospholipasecontaining domain 3; Pediatric obesity; Adipose Tissue; Adolescent; Alanine Transaminase; Alleles; Child; Child, Preschool; Fatty Acids, Unsaturated; Fatty Liver; Female; Heterozygote; Humans; Inflammation; Lipase; Liver; Male; Membrane Proteins; Odds Ratio; Pediatric Obesity; Receptors, G-Protein-Coupled; Genotype; Polymorphism, Genetic, Odds Ratio, Humans, Child, Alleles, Inflammation, Polymorphism, Genetic, Membrane Proteins, Alanine Transaminase, Lipase, Fatty Liver, Adipose Tissue, Liver, Child, Preschool, Fatty Acids, Unsaturated, Female
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