title: Novel association between a nonsynonymous variant (R270H) of the G-protein-coupled receptor 120 and liver injury in children and adolescents with obesity.
abstract: The 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.
authors.affiliation: Department of Woman, Child, and General and Specialized Surgery, Seconda Univesità degli Studi di Napoli, Napoli, Italy.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Marzuillo
authors.forename: Anna
authors.initials: A
authors.lastname: Grandone
authors.forename: Mariasole
authors.initials: M
authors.lastname: Conte
authors.forename: Francesco
authors.initials: F
authors.lastname: Capuano
authors.forename: Grazia
authors.initials: G
authors.lastname: Cirillo
authors.forename: Anna
authors.initials: A
authors.lastname: Di Sessa
authors.forename: Giuseppina R
authors.initials: GR
authors.lastname: Umano
authors.forename: Roberta
authors.initials: R
authors.lastname: Romano
authors.forename: Laura
authors.initials: L
authors.lastname: Perrone
authors.forename: Emanuele Miraglia
authors.initials: EM
authors.lastname: del Giudice
mesh_terms: D000273:Adipose Tissue / Q000473:pathology; D000293:Adolescent; D000410:Alanine Transaminase / Q000097:blood; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D005231:Fatty Acids, Unsaturated / Q000235:genetics; D005234:Fatty Liver / Q000209:etiology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000235:genetics; D008049:Lipase / Q000235:genetics*; D008099:Liver / Q000201:enzymology / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D016017:Odds Ratio; D063766:Pediatric Obesity / Q000150:complications / Q000235:genetics*; D011110:Polymorphism, Genetic; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D000410:Alanine Transaminase; D005231:Fatty Acids, Unsaturated; D008049:Lipase; D008565:Membrane Proteins; D043562:Receptors, G-Protein-Coupled; C519853:FFAR4 protein, human; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent